Search

Introduction: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Methods: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Results: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Discussion: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Conclusions: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Graphical Abstract: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst. [ABSTRACT FROM AUTHOR]

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today's scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Methods Eligible patients (average pain intensity [numerical rating scale-3 ( NRS-3)] ≥6; pain DETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval ( RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). Results For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in pain DETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). Conclusions The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component. [ABSTRACT FROM AUTHOR]

Abstract: Background: In 2001, a transdermal matrix patch formulation of buprenorphine was approved for the treatment of moderate to severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. The primary recommendation contained in the prescribing information was that transdermal patches be worn for a 3-day period before application of a new patch. Objective: This study was conducted to evaluate the potential for extending the time the buprenorphine patch is worn from 3 to 4 days. Methods: This single-center, randomized, open-label, crossover Phase III study compared the efficacy and tolerability of the buprenorphine transdermal patch applied for different durations, with patch changes every 3 days versus every 4 days (12 days each), in patients with chronic moderate or severe pain of malignant or nonmalignant origin. Study participants were aged >18 years, had already responded to at least 4 weeks of transdermal buprenorphine, and had achieved steady-state conditions for at least 2 weeks before enrollment. The primary end point was patients’ rating of the quality of treatment (analgesic efficacy and tolerability, rated on a 5-point scale: very good, good, satisfactory, poor, and inadequate) at the completion of each treatment regimen. Also recorded were physicians'' ratings of the quality of treatment; pain intensity, rated on an 11-point numerical rating scale (from 0 = no pain to 10 = worst pain imaginable) and on the McGill Pain Questionnaire (MPQ) (maximum pain = 3.0); health status, assessed using the 36-item Short Form Health Survey (SF-36), expressed as a percentage of the best health condition (100%); and pain relief (5-point scale: complete, good, satisfactory, slight, and none). Local skin tolerability was evaluated for objective and subjective dermatologic symptoms at the patch application sites. Patients recorded daily pain intensities at specified times of day and night, pain relief (5-point verbal rating scale), and sleep duration (<2 hours, >2–3 hours, >3-<6 hours, or >6 hours) in a diary. The safety profile was evaluated based on standard monitoring of adverse events, vital signs, and routine laboratory tests. Results: Forty-nine white patients (25 women, 24 men) were enrolled; their mean (SD) age was 61.6 (11.5) years, and their mean weight was 74.7 (16.7) kg. The most common source of pain was musculoskeletal disorders (40 patients), followed by nervous system disorders (10), neoplasms (9), injuries (5), and other causes (6). Forty-one patients completed the study; 2 patients discontinued because of adverse events, 1 because of lack of efficacy, and 5 for nonmedical reasons. Thirty-three patients provided data per protocol. Patients in the perprotocol population received a mean (SD) transdermal buprenorphine dose of 49.9 (38.9) pg/h. The proportion of patients in the per-protocol population rating the quality of treatment as adequate (combined ratings of very good, good, and satisfactory) was 93.9% (31/33) for both regimens. The physicians'' ratings indicated adequate quality of treatment in 93.8% (30/32) of patients applying 4 patches for 3 days each and 97.0% (32/33) of patients applying 3 patches for 4 days each. Mean (SD) pain intensity scores on the numerical rating scale were similar after completion of the 3− and 4-day regimens (3.73 [1.88] and 3.88 [1.75] points, respectively), as were MPQ scores (0.79 [0.67] and 0.79 [0.78]). The mean (SD) proportion of days with at least satisfactory pain relief was 83.9% (26.1%) and 85.6% (24.4%) for the 3- and 4-day regimens; the corresponding proportions of nights with at least satisfactory pain relief were 85.2% (26.6%) and 88.1% (21.4%). Continuously assessed pain intensities at specified times of day and night (numerical rating scale) did not differ significantly between regimens. Mean SF-36 health status scores did not differ significantly between regimens (total score: 37.7% [17.0%] and 37.7% [17.3%]). Mean rates of nights with good sleep quality were 28.5% (39.9%) for the 3-day regimen and 36.0% (42.6%) for the 4-day regimen. Local skin tolerability was comparable for the 3− and 4-day regimens, with objective findings (mainly erythema) at the patch-application sites in 17 of 32 and 11 of 33 patients, respectively, and subjective symptoms (mainly itching) in 16 of 32 and 13 of 33 patients. The most common adverse events in the safety population were nausea, dizziness/giddiness, and malaise/fatigue (3/49 [6.1%] each). Conclusion: Analgesic efficacy, patients'' satisfaction with the quality of treatment, and skin tolerability did not differ significantly between 3 and 4 days of patch application in these patients with chronic pain who had been previously stabilized on transdermal buprenorphine. [Copyright &y& Elsevier]

Abstract: Background:: Tramadol is widely prescribed, even to the eldest patients. Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages. Objective:: The aim of this study was to explore the effectiveness, PK properties, and safety profile of 2 galenic tramadol formulations in 3 similarly sized age groups with malignant and nonmalignant pain of moderate to severe intensity. Methods:: This prospective, age-group-controlled study was conducted at the ambulatory pain clinic of the Landeskrankenhaus Kärnten, Klagenfurt, Austria. Male and female adults with malignant and nonmalignant pain of moderate to severe intensity were eligible. Patients were stratified into similarly sized age groups, as follows: ≥75, 65-<75, and <65 years. Patients first received the immediate-release galenic formulation of tramadol (tramadol IR) until steady state was achieved, followed by the sustained-release formulation (tramadol SR) until steady state. Serum concentrations of tramadol and its active metabolite (O-desmethyl-tramadol [M1]) were measured using gas chromatography to estimate the age-related PK handling of the analgesic drug. Three validated scales were used to measure pain intensity during the study: a 100-mm visual analog scale (VAS), an 11-point numeric analog scale (NAS), and a 4-point verbal rating scale (VRS). Tolerability was assessed by evaluating daily answers about the potential occurrence of adverse events (and respective details such as type and severity) from baseline until the end of the observation period. Results:: A total of 100 patients were enrolled (58 women, 42 men; mean [SD] age, 65.2 [15.0] years; ≥75, 30 patients; 65-<75, 31 patients; and <65 years, 39 patients). Predominant causes of pain were neoplasms (27.4% of causes) and injury and other external causes (20.8%), and diseases of the musculoskeletal and connective-tissues systems (19.8%). Fifty-five patients completed the study and provided all data as planned. Mean (SEM) steady-state tramadol IR doses were 250 (20.2), 277 (39.8), and 325 (33.1) mg/d in patients aged ≥75, 65-<75, and 65 years, respectively (P = NS); tramadol SR, 278 (27.5), 306 (39.7), and 340 (35.1) mg/d (P = NS). Serum concentrations of tramadol and M1 were statistically similar across all 3 age groups. Overall, mean pain intensity scores, as measured using the VAS and NAS, were decreased from baseline (62.4 [2.0] mm and 6.22 [0.22] points, respectively) to steady state with tramadol IR (23.6 [2.9] mm and 2.65 [0.30] points) and tramadol SR (16.9 [2.5] mm and 1.91 [0.26] points) (all, P < 0.001). Pain intensity before and improvements during both treatment phases were similar across all 3 age groups. Results:: for pain intensity on the VRS also did not find age-related differences. The predominant adverse effects were nausea (27.0% of patients), dizziness and giddiness (18.0%), and malaise and fatigue (15.0%); no significant differences in adverse events were found between age groups. Conclusions:: The fate of tramadol and its active metabolite, and their clinical effects, have been examined here for the first time in a prospective cohort study, which compared patients aged <65 years, 65-<75 years, and ≥75 years. In contrast to expecta tions, it was concluded that tramadol IR and tramadol SR were both generally well tolerated and effective in the treatment of moderate to severe pain in any of the 3 age groups in these patients. Although the eldest group of patients consumed, on average, 20% less tramadol (P = NS) than the youngest group, the PK properties of both drugs were not changed when given to elderly patients. [Copyright &y& Elsevier]

Background:: Transdermal buprenorphine is available in Europe for the treatment of moderate to severe chronic pain. It has been evaluated at doses of 35, 52.5, and 70 μg/h for the management of moderate to severe chronic cancer and noncancer pain in 3 randomized, double-blind, placebo-controlled trials, each of limited duration (∼14 days each). Long-term data are essential to determining the performance of an analgesic in the management of chronic pain. Objective:: The purpose of this follow-up study was to obtain data on the efficacy and tolerability of long-term treatment with transdermal buprenorphine in cancer and noncancer patients with chronic persistent pain of moderate to severe intensity. Methods:: This was an open-label, uncontrolled, follow-up study in patients from the 3 previous clinical trials who elected to continue treatment with transdermal buprenorphine 35 μg/h and sublingual buprenorphine tablets (0.2 mg) as needed for breakthrough pain. The patch was to be changed every 72 hours throughout the patient''s course of pain therapy. At visits every 2 weeks for the first 4 weeks and every 4 weeks for the remainder of study participation, patients evaluated their pain relief retrospectively on a 4-point verbal rating scale. They also rated the ease of patch handling using a 3-point verbal rating scale. Patterns of dose escalation and dose stability were monitored over time. Adherence to therapy was determined based on the number of patients who complied with the dosing schedule. Adverse events were documented by type, intensity, location (systemic or local), and relationship to study medication. Results:: Two hundred thirty-nine patients were included in this follow-up study (120 women, 119 men; 100% white; mean [SD] age, 58 [11.3] years; mean weight, 70.8 [14.7] kg). One hundred thirty-four had cancer-related pain and 105 had pain of noncancerous origin. The mean duration of participation was 7.5 months, and 37 (15.5%) patients participated for >12 months. Maximum study participation was 3.4 years in cancer patients and 5.7 years in noncancer patients. One hundred eighty-eight (78.7%) patients were considered adherent to therapy. The majority (65.9%) of patients managed their pain with the patchalone or took no more than 1 additional sublingual tablet daily for breakthrough pain. At least satisfactory pain relief was reported by 215 (90.0%) patients, and the buprenorphine patch was generally well tolerated. The most common systemic adverse drug reactions were nausea (9.2%), dizziness (4.6%), vomiting (4.2%), constipation (3.8%), and tiredness (2.9%), whereas the most common local adverse drug reactions were erythema (12.1%), pruritus (10.5%), and exanthema (8.8%). Conclusion:: Transdermal buprenorphine was generally well tolerated and effective for the long-term treatment of chronic cancer or noncancer pain in these patients who had previously received buprenorphine in 3 short-term clinical trials. [Copyright &y& Elsevier]

Purpose: Patients in the ICU after long-term administration of an opioid/hypnotic often develop delirium. To assess the nature of this phenomenon, patients in a surgical ICU following ventilatory support and sedation with an opioid/hypnotic/sedative were studied.Methodology: Following sufentanil/midazolam (group 1; n =14) or sufentanil/propofol (group 2; n =15) sedation, patients were evaluated for changes in mean arterial blood pressure and heart rate, the activity of the central nervous system (sensory evoked potentials, spectral edge frequency of EEG), and the endogenous opioids plasma concentrations (beta-endorphin, met-enkephalin). Data obtained were correlated with the individual intensities of withdrawal symptoms 6-, 12-, and 24 h following sedation.Results: Following a mean duration of ventilation of 7.7 days (+/-3.6 SD) in groups 1 and 3.5 (+/-1.7 SD) in group 2, withdrawal intensities peaked within the 6th hour after cessation. Plasma beta-endorphin and met-enkephalin levels were low during sedation, and only the sufentanil/midazolam group demonstrated a postinhibitory overshoot. Withdrawal symptom intensities demonstrated an inverse correlation with beta-endorphin and met-enkephalin levels, a direct linear correlation with amplitude height of the evoked potential, and blood pressure and heart rate changes. Withdrawal intensities did not correlate with EEG power spectral edge frequency.Conclusion: The endorphinergic system is suppressed when a potent exogenous opioid like sufentanil is given over a long period of time. Following sedation, abstinence symptoms seem to be related to postinhibitory increased endorphin synthesis. This is mostly seen in the combination of sufentanil/midazolam. In addition, an increase in the amplitude of the sensory-evoked potential suggests a postinhibitory excitatory state within the nociceptive system. [ABSTRACT FROM AUTHOR]

Abstract: Background:: The equipotency ratio of transdermal (TD) fentanyl to oral morphine has been established as 1:100; for buprenorphine TD, a ratio of 1:75 has been proposed, although this ratio has not been confirmed in clinical studies. Growing evidence from clinical practice, in which much lower doses of buprenorphine are used, suggests that this conversion ratio may be too high. Objective:: The aim of this study was to comparecalculated equipotent oral morphine doses of fentanyl TD with equipotent oral morphine doses of buprenorphine TD prescribed in clinical practice. Methods:: This retrospective study identified patientswith cancer and noncancer pain who had received ≥1 prescription for fentanyl TD or buprenorphine TD (the all-patients groups) from the German IMS Disease Analyzer-mediplus database, which contains all relevant data concerning drug prescriptions from 400 practices in Germany. Also identified were subgroups of the all-patients groups who had received long-term treatment with fentanyl TD or buprenorphine TD and were considered to have similar pain intensity, as they had previously received similar analgesic medication (the identical-cohort groups). Mean prescribed daily doses for the all-patients and identical-cohort groups were calculated based on the distribution of prescribed patch strengths. Because patients could have applied >1 patch, mean prescribed daily doses were also calculated based on an assumption of double application when appropriate. Equipotent oral morphine doses were estimated using equipotency ratios of 1:100 for fentanyl TD and 1:75 for buprenorphine TD. Results:: The all-patients groups consisted of 2198 patients with noncancer pain and 2544 patients with cancer pain; the identical-cohort groups consisted of 380 patients with noncancer pain and 496 patients with cancer pain (529 women, 347 men; mean age, 74 years [range, 25–101 years]). Equipotent doses of oral morphine were significantly lower in patients receiving buprenorphine TD compared with those receiving fentanyl TD (P &#60; 0.001). In cancer patients, the equipotent oral morphine doses of fentanyl TD and buprenorphine TD were 130.9 to 138.9 mg and 85.2 to 88.8 mg, respectively; in noncancer patients, the corresponding values were 117.0 to 118.3 mg and 80.2 to 80.9 mg. Based on these results, an equipotency ratio of 1:110 to 1:115 for buprenorphine TD would appear to be more appropriate than the proposed ratio of 1:75. Conclusions:: The fact that this retrospective analysis conducted in identical cohorts showed lower calculated equipotent oral morphine doses in the buprenorphine TD groups compared with the fentanyl TD groups calls into question the proposed 1:75 ratio for conversion of buprenorphine TD to equipotent oral morphine doses. Based on the findings of the present study, an equipotency ratio of 1:110 to 1:115 may be more appropriate. However, confirmative data from prospective randomized clinical trials are needed. [Copyright &y& Elsevier]

Objective.—To evaluate the efficacy of aspirin for headache when exercising during acute high-altitude exposure. Background.—Aspirin effectively prevents headache when mostly resting during acute high-altitude exposure. However, the majority of individuals exposed to high altitude perform mountaineering activities, which might trigger headache. Design.—Randomized, double-blind, placebo-controlled trial. Methods.—Thirty-one healthy volunteers (20 men, 11 women; aged 22 to 59 years) were transported to an altitude of about 3000 meters and climbed up to 3800 meters. They then descended to a mountain hut at 3480 meters and spent 2 nights there. Tablets (placebo or 320 mg aspirin) were administered three times at 4-hour intervals, beginning 2 hours before arrival at high altitude. Headache scoring and measurements of heart rate, blood pressure, and arterial oxygen saturation were performed. Results.—Ninety-three percent (14 of 15) of the placebo group and 56% (9 of 16) of the aspirin group developed headache when mountaineering activities were performed during acute exposure to high altitude (P<.05). Five hours after arrival at high altitude, mean resting oxygen saturation was 86.1% ± 2.1% with aspirin and 85.7 % ± 2.8% with placebo (P = .66). However, subjects in the aspirin group developed headache at saturation values less than or equal to 86%, while those in the placebo group developed headache at saturation values less than 90%. Conclusions.—Although the prophylactic intake of about 1 gram of aspirin reduced the headache incidence when exercising during acute high-altitude exposure, the incidence of headache was higher than previously shown for resting conditions. Aspirin resulted in tolerance to lower arterial oxygen saturation without development of headache; exercise had the opposite effect. [ABSTRACT FROM AUTHOR]

Introduction: Ganglionic local opioid analgesia (GLOA) at the superior cervical ganglion (SCG) is performed for pain control and is known to be an effective procedure. In this study, we evaluated the spread of the injectate in the area of the SCG. Our expectation was that there would be a correlation between the area and volume of the injectate spread and post-procedural outcome measures. Methods: This was a retrospective blinded review of magnetic resonance imaging (MRI) scans. Assessors evaluated the anatomical area of fluid spread, the furthermost spread from midline, any hampered spread and contact of contrast fluid with other structures. The efficacy of GLOA and complications were estimated. Results: The main solution spread reached from the C1 to C3 vertebrae. The furthest spread in the lateral and sagittal planes was 21.2 and 15.2 mm, respectively. The furthest craniocaudal spread was 63.5 mm. In 53.3% and 33% of interventions, the solution was found in the parapharyngeal space and in its "medial compartment," respectively. A correlation was found between pain relief and both solution spread and volume of solution spread. No hampered spread was recorded. A negative correlation between pain reduction and number of GLOA was observed. Higher pre-procedural pain intensity was correlated with higher pain reduction. We estimated pain relief in 93% of procedures correctly. No correlation between post-procedural Numerical Rating Scale (NRS) scores and different needle approaches was found. Conclusion: For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures. A total volume of 2 ml injected into the parapharyngeal space and its "medial compartment" is recommended. Higher volumes may lead to uncontrolled distribution patterns. Trial registration: Clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31. Plain Language Summary: The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed "ganglionic local opioid analgesia" (GLOA). This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient's quality of life, such as trigeminal neuralgia. For example, as part of a multimodal approach for pain management, GLOA at the superior cervical ganglion should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores. [ABSTRACT FROM AUTHOR]

Background : Additional benefits of passive exposures to intermittent hypoxia and hyperoxia on cognitive performance and functional exercise capacity have been demonstrated in geriatric patients who performed a multimodal training program. The main goal of the present study was to evaluate effects of adding intermittent hypoxic-hyperoxic training (IHHT) to a multimodal training intervention (MTI) on mobility and perceived health in old individuals at a Geriatric Day Hospital. Methods: Thirty-four patients between 64 and 92 years participated in the double blind, randomized and controlled clinical trial. The elderly patients attended in a 5-7 weeks lasting MTI (strength, endurance, balance, reaction, flexibility, coordination, and cognitive exercises) and performed IHHT (breathing 10-14% oxygen for 4-7 min followed by 2–4 min 30–40% oxygen) in the Hypoxic Group (HG) or placebo treatment with ambient air in the Normoxic Group (NG) in parallel. Before and after all treatments, mobility was assessed by the Tinetti Mobility Test (TMT), the Timed-Up-and-Go Test (TUG) and Barthel-Index, while perceived health was assessed by one part of the EQ-5D Test, the EQ visual analogue scale (EQ VAS). Results: After the MTI plus IHHT or normoxia sessions, results of the TMT, TUG, Barthel Index and EQ-VAS revealed no significant difference between HG and NG (+ 14.9% vs + 15.4%, p = 0.25; - 21% vs - 26.3%, p = 0.51; + 4.2% vs+ 3.6%, p = 0.56; + 37.9% vs+ 33.9%, p = 0.24;). Conclusions: IHHT added to MTI did not elicit additional improvements in perceived health and mobility compared to MTI alone. [ABSTRACT FROM AUTHOR]

Presents information on transdermal buprenorphine, an effective analgesic in the treatment of acute and chronic pain. Benefits of a transdermal delivery system; Requirements in treating pain; Features and properties of buprenorphine transdermal system.

Presents information on a study examining the efficacy of aspirin as prophylaxis against headache at high altitudes. Subjects of the study; Methodology used in the study; Reason for the increasing incidence of high altitude headache.

Introduction: Computed tomography (CT)-guided coeliac plexus neurolysis (CPN) is considered effective at controlling pain in patients with intra-abdominal malignancies. The primary objective was to correlate pain outcomes with the spread of neurolytic solution in the coeliac area and to evaluate the predictive value for the spread of injectate for pain outcomes and side effects. Methods: Blinded CT scans were reviewed. The coeliac area was divided into nine quadrants. Assessors evaluated quadrants according to contrast spread, needle tip position, and the contact between the injectate and other organs and plexuses. Efficacy of CPN and complications were estimated. Results: In 54.9% there was complete spread of the neurolytic in the coeliac area with no correlation between pain relief and spread of injectate. In 85% the neurolytic had contact with viscera with no correlation with pain relief or complications. There was no correlation between needle tip position and spread of the neurolytic and contact of the neurolytic with viscera. In 71.6% the injectate was found to have spread into "other" plexuses. In 13.3% hampered spread of the injectate was observed. There was no correlation between patterns of injectate spread and pain relief, pain relief and spread of injectate in any particular quadrants, and expected and documented post-procedural pain scores. Conclusions: Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. Plain language summary: CT-guided coeliac plexus neurolysis is considered effective at controlling pain in patients with intra-abdominal malignancies. Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. [ABSTRACT FROM AUTHOR]

Reports on the use of a transdermal therapeutic system containing buprenorphine to manage pain. Avoidance of gastrointestinal passage and first-pass metabolism; Continuous slow release of buprenorphine at a defined rate from its polymer matrix into the blood; Efficacy and safety of transdermal buprenorphine.

Introduction: Prevalence rates of chronic abdominal pain (CAP) and breakthrough cancer pain (BTcP) are high in patients with intra-abdominal malignancies. As part of a multimodal approach, CT-guided coeliac plexus blockade (CPB) and CT-guided coeliac plexus neurolysis (CPN) are commonly used pain management strategies. The aim of this study was to evaluate pain outcomes among patients with intra-abdominal malignancies who underwent CPB and/or CPN. Methods: Patients with intra-abdominal malignancies who underwent CPB and/or CPN for pain control at the general hospital Klagenfurt am Wörthersee from 2010 to 2019 were enrolled. Results: A total of 84 procedures (24 CPB and 60 CPN) were performed on 52 patients; 62% of these patients had pancreatic cancer. CPN led to significant pain reduction and decreased BTcP intensity. Patients receiving repeated CPN showed higher individual pain reduction. Higher pre-procedural pain intensity was correlated with higher pain reduction. No difference in pain reduction in patients receiving a diagnostic CPB prior to CPN compared to patients without a diagnostic CPB was found. Higher pain reduction after CPN led to longer-lasting pain relief. The time frame from diagnosis to CPN was 472 (± 416) days. Patients experienced a mean duration of pain prior to CPN of 330 (± 53) days. The time frame from diagnosis to CPN was shorter in patients with pancreatic cancer compared to other intra-abdominal malignancies. In 58% of patients pain medication was stable or was reduced after CPN; 16% of patients complained about pain during the procedure; no major complications occurred. There was no correlation between median survival after CPN and pain outcomes. Conclusions: In patients with intra-abdominal malignancy-related CAP, CPN is a safe and effective procedure which can provide long-lasting significant relief of background pain and BTcP. As part of a multimodal approach, CPN should be considered as an earlier option for pain management in these patients. Plain Language Summary: In patients with intra-abdominal malignancy-related abdominal pain, CT-guided coeliac plexus neurolysis is a safe and effective procedure. It can provide long-lasting significant relief of background pain and breakthrough cancer pain. As part of a multimodal approach, coeliac plexus neurolysis should be considered as an earlier option for pain management in patients with intractable abdominal cancer pain. [ABSTRACT FROM AUTHOR]

Background: Buprenorphine is a potent opioid analgesic that is available in sublingual and parenteral formulations. A new formulation, buprenorphine transdermal delivery system (TDS), has been developed.Objective: The aim of this study was to compare the analgesic efficacy and tolerability of the 3 available dosages of buprenorphine TDS (35.0, 52.5, and 70.0 μg/h) with placebo.Methods: This was a randomized, double-blind, placebo-controlled, multicenter study. Patients with chronic, severe pain related to cancer or other diseases and inadequately controlled with weak opioids were randomized to receive buprenorphine TDS 35.0, 52.5, or 70.0 μg/h or placebo patch for up to 15 days. A new patch was applied every 72 hours, for a total of 5 patches. All patients were permitted rescue analgesia with sublingual buprenorphine tablets (0.2 mg) as required for breakthrough pain.Results: A total of 157 patients (86 women, 71 men; mean [SD] age, 58.7 [11.8] years) were initially enrolled in the study. Buprenorphine TDS was associated with significantly higher response rates than was placebo at the 35.0- and 52.5-μg/h dosages (36.6% and 47.5%, respectively, vs 16.2%; P=0.032 and P=0.003, respectively) and a numerically higher response rate at 70.0 μg/h (33.3%), although this difference did not reach statistical significance. Patients treated with buprenorphine TDS experienced a 56.7% reduction in use of sublingual rescue analgesic during the study compared with an 8% reduction with the placebo patch. A total of 43.5% of patients treated with buprenorphine TDS reported good or complete pain relief compared with 32.4% in the placebo group. Pain intensity decreased in a dose-dependent manner with buprenorphine TDS, and the duration of sleep uninterrupted by pain was improved by the end of the study. More than three fourths (78.8%) of patients in the placebo and buprenorphine TDS groups reported at least 1 adverse event (AE) during the study. The most common AEs were central nervous system and gastrointestinal symptoms. The majority of treatment-related AEs were mild or moderate in intensity and were typical of those occurring at the beginning of therapy with a strong opioid.Conclusions: Buprenorphine TDS was shown to be an effective analgesic against chronic, severe pain in this study population. Patients treated with this new formulation of buprenorphine showed improved duration of sleep and reduced need for additional oral analgesics. [Copyright &y& Elsevier]

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI − 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155–170] min for chloroprocaine versus 380 [209–450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile. Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria—BASG). [ABSTRACT FROM AUTHOR]

This article summarizes recommendations made by six pain specialists who discussed the rationale for ziconotide intrathecal analgesia (ITA) and the requirement for evidence‐based guidance on its use, from a European perspective. Riemser Pharma GmbH (Greifswald, Germany), which holds the European marketing authorization for ziconotide, hosted the meeting. The group agreed that ITA is under‐used in Europe, adding that ziconotide ITA has potential to be a first‐line alternative to morphine; both are already first‐line options in the USA. Ziconotide ITA (initiated using a low‐dose, slow‐titration approach) is suitable for many patients with noncancer‐ or cancer‐related chronic refractory pain and no history of psychosis. Adopting ziconotide as first‐line ITA could reduce opioid usage in these patient populations. The group advocated a risk‐reduction strategy for all candidate patients, including compulsory prescreening for neuropsychosis, and requested US–European alignment of the licensed starting dose for ziconotide: the low‐and‐slow approach practiced in the USA has a better tolerability profile than the fixed high starting dose licensed in Europe. Of note, an update to the European Summary of Product Characteristics is anticipated in early 2021. The group acknowledged that the Polyanalgesic Consensus Conference (PACC) treatment algorithms for ziconotide ITA provide useful guidance, but recommendations tailored specifically for European settings are required. Before a consensus process can formally begin, the group called for additional European prospective studies to investigate ziconotide in low‐and‐slow dosing strategies, in different patient settings. Such data would enable European guidance to have the most appropriate evidence at its core. [ABSTRACT FROM AUTHOR]

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective analysis was to evaluate the clinical feasibility of the supraclavicular ultrasound‐guided cannulation of the brachiocephalic vein in infants weighing less than 1500 g. Methods: The ultrasound probe was placed in the supraclavicular region so as to obtain the optimum sonographic long‐axis view of the brachiocephalic vein. By using an in‐plane approach the brachiocephalic vein was cannulated by using a 24‐gauge intravenous cannula under real‐time ultrasound guidance into the vein followed by the insertion of a 2‐French single lumen catheter using the Seldinger technique. Results: Forty‐six brachiocephalic vein cannulations in infants weighing between 0.55 and 1.5 kg (Median: 1.2; 95%‐CI: 0.9‐1.2) were included. Ultimate success rate was 89.1% (41 out of 46). One cannulation attempt was required in 30 (65.2%) patients, 2 in 6 (13%) and 3 in 5 (10.8%), respectively. Smaller weight babies did not require significantly more cannulation attempts. The probability of successful cannulation on the first attempt increased significantly from 40% (2010) to more than 80% (2019) over the time course of this series. Median catheter dwell time was 15 days (95%‐CI: 9‐20) with one catheter being removed prematurely after 8 days due to obstruction. Conclusion: Supracalvicular in‐plane real‐time ultrasound‐guided cannulation of the brachiocephalic vein seems to be a convenient and feasible option to provide large‐bore central venous access for very small and sick babies. [ABSTRACT FROM AUTHOR]

Objective: To identify variables that influence pain reduction following peripheral nerve field stimulation (PNFS) in order to identify a potential responder profile. Methods: Exploratory univariate and multivariate (random forest) analyses were performed separately on 2 randomized controlled trials and a registry; all included patients with chronic back pain, mainly failed back surgery syndrome. An international expert panel judged the clinical relevance of variables to identify responders by consensus. Results: Variables identified that may help predict PNFS success in patients with back pain include patient and pain characteristics (age, time since onset of pain and spinal surgery, pain medication history, position and size of pain area, pain severity, mixed nociceptive/neuropathic pain, health‐related quality of life, depression, functional disability, and leg pain status), implant procedure variables (the number and position of leads, paresthesia coverage, and amount of pain relief during the trial), and programming (number of programs, cathodes, and anodes; pulse rate; pulse width; and percentage of device usage). Conclusions: While these analyses are exploratory and restricted to a limited sample size, they suggest variables that may play a role in predicting a therapeutic response. These results, however, are informative only and should be cautiously interpreted. Future research to validate the variables in a clinical study is needed. [ABSTRACT FROM AUTHOR]

Objective: Dysphagia is a common disorder in neurological and non-neurological intensive care unit (ICU) patients and can lead to aspiration pneumonia, prolonged ventilation, and delayed extubation. Dysphagia is an independent predictor of increased mortality. In dysphagic stroke patients with tracheotomy, the use of pharyngeal electric stimulation (PES), an emerging technique to treat dysphagia, has been shown to improve airway protection and shorten time to decannulation. The objective of this study was to determine whether patients who receive PES have a lower prevalence of pneumonia and frequency of reintubation.Design: Secondary analysis of a non-blinded interventional subject sample from a large clinical study with a historical age, pathology, and severity-matched control group.Setting: ICU of a tertiary care medical center.Patients: In this pilot non-blinded study, a group of 15 intubated patients in a general and a neurologic ICU received PES while orally intubated during ICU stay. A control group (n = 25) matched for age, type, and region of pathology, and severity of illness expressed by Simplified Acute Physiology Score and Therapeutic Intervention Scoring System was used to compare for pneumonia and need for reintubation.Main Results: Patients treated with PES had significantly lower prevalence of pneumonia (4 vs 21, p = 0.00046) and frequency of reintubation (0 vs 6, p = 0.046) when compared to controls.Conclusion: Although limited by its small size and non-blinded design, this is the first study demonstrating the benefits of PES in ICU patients still orally intubated, thus offering a potential new method to reduce morbidity, mortality, and economic burden in a mixed ICU population. In order to further investigate and strengthen our findings, a statistically powered, randomized controlled study is recommended. [ABSTRACT FROM AUTHOR]

Presents a case of postoperative apnea, possibly caused by caudal clonidine in a neonate undergoing inguinal herniorrhaphy, who received a combination of light inhalation anesthesia plus caudal block with rapivacaine and clonidine. Absence of apparent risk factors for postanesthetic apnea in the patient; Minor abnormalities observed during oxycardiorespirography several days after surgery; Conclusion that clonidine caused postanesthetic apnea in the neonate.

The importance of arterial oxygen saturation for the prediction of acute mountain sickness (AMS) is still a matter of debate. Reasons for discrepancies may result from varying laboratory or field conditions and their interactions. Thus, we analyzed data from our prior high-altitude studies, including participants of a broad range of age of both sexes (20 males and 20 females, aged between 20 and 67 years) under strictly standardized conditions of pre-exposure and acute exposure to real high altitude (3480 m). A set of resting cardiovascular, respiratory, hematological, and metabolic variables were recorded at high altitude (Testa Grigia, Plateau Rosa, 3480 m; Swiss-Italian boarder) after performing pretests at low altitude (Innsbruck, 600 m, Austria). Our analyses indicate that (1) smaller changes in resting minute ventilation (VE) and a larger decrease of peripheral oxygen saturation (SpO2) during the first 3 hours of acute exposure to high altitude were independent predictors for subsequent development of AMS (90% correct prediction), (2) there are no differences of responses between sexes, and (3) there is no association of responses with age. Considering the independent effects of both responses (VE and SpO2) may be of clinical/practical relevance. Moreover, the presented data derived from a broad age range of both sexes might be of interest for comparative purposes. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective analysis was to evaluate the clinical effectiveness of the supraclavicular ultrasound-guided cannulation of the brachiocephalic vein in preterm infants.Methods: The ultrasound probe was placed in the supraclavicular region so as to obtain the optimum sonographic long-axis view of the brachiocephalic vein. By using a strict in-plane approach the brachiocephalic vein was cannulated by advancing a 22- or 24-gauge iv cannula from lateral to medial under the long axis of the ultrasound probe under real-time ultrasound guidance into the vein.Results: One hundred and forty-two cannulations in infants weighing between 0.59 and 2.5 kg (median: 2.1; CI: 2.0 to 2.2) were included. Ultimate success rate was 94% (134 of 142). One cannulation attempt was required in 100 (70%) patients, two attempts in 21 (15%), and three attempts in 13 (9%). The smaller the weight of the infant the more attempts were needed. More attempts also were needed for the right brachiocephalic vein, which was primarily targeted in 75 (53%) neonates. One (1%) inadvertent arterial puncture was noted.Conclusions: This supraclavicular, in-plane, real-time, ultrasound-guided cannulation of the brachiocephalic vein seems to be a convenient and effective method to insert central venous catheters in preterm infants. [ABSTRACT FROM AUTHOR]

Keywords: Altitude; systemic blood pressure; sex differences EN Altitude systemic blood pressure sex differences 1 2 2 08/24/22 20220701 NES 220701 Teaser Proper regulation of the systemic blood pressure is crucial for human health and may be affected in changing environmental conditions, e.g. during high-altitude exposure. Travelling to high altitude, i.e. >2500 m, increases systemic blood pressure (BP) at rest and during exercise in normotensive and hypertensive subjects.[1] Although sex differences in BP regulation are well established,[2] evidence on the interaction with acute high-altitude exposure is scarce. Heart rate (HR) and peripheral oxygen saturation (SpO SB 2 sb ) were determined by finger pulse oximetry (Onyx, NONIN) and systemic BP by the use of a wrist blood pressure monitor (OMRON R3). [Extracted from the article]

Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium. [ABSTRACT FROM AUTHOR]

Background The supraclavicular ultrasound ( US)-guided cannulation of the brachiocephalic vein ( BCV) is one option of central venous line placement in infants. Aim The aim of this prospective study was to evaluate whether there was an association between the optimum ultrasonographic view as obtained of the entire longitudinal extension of the right BCV and the ease of supraclavicular cannulation when using a strict in-plane technique via a linear US probe in small infants. Methods The US probe was placed in the right supraclavicular region. If the optimum obtainable sonographic view presented the entire longitudinal extension of the right BCV demonstrating clearly its path caudally alongside the pleura, it was graded as I. If, however, only a circular view, i.e., the initial part of the right BCV was obtainable via US, it was graded as II. The right BCV was cannulated by advancing a 22-gauge i.v. cannula from lateral to medial strictly under the long axis of the US probe under direct US vision into the vein. Results Seventy-nine infants weighing between 0.8 and 4.5 kg (Median: 3.4 ± 0.09) were included. In 50 (63.3%) patients, the sonographic view was graded as I and in 29 (36.7%) as II. The proportion of patients successfully cannulated on the first attempt was significantly smaller in patients graded as II, i.e., circular, sonographic view of the right BCV than in patients graded as I, i.e., sonographic view of the entire longitudinal extension of the right BCV (41% vs 90%; chi-square analysis: P < 0.01). Conclusion The sonographic view obtainable of the entire longitudinal extension of the right BCV resulted in significantly fewer required cannulation attempts. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the applicability of US-guided rectus sheath block and to find out the efficacy of analgesia provided using this method without the need for opioids in conventional Hypertrophic pyloric stenosis (HPS) surgery in infants. Background: This study describes the provision of intra- as well as postoperative analgesia by the use of an ultrasound-guided rectus sheath block in infants undergoing conventional HPS surgery under general anesthesia. Methods/Materials: The anesthetic protocols of 26 infants undergoing HPS surgery were reviewed retrospectively. Results: The weight of the infants ranged from 2.6 to 4.6 kg. The rectus sheath block was regarded as successful in all patients as there was no heart rate increase upon surgical skin incision in any of the patients. Two out of 26 (7.6%) babies needed additional intraoperative rescue analgesia and were administered fentanyl at 20 and 40 min after skin incision. Two more (a total of 4; 15.3%) babies required postoperative analgesia and were administered tramadol droplets and liquid ibuprofen at 15, 120 and 150 min postoperatively. Duration of surgery was significantly longer in those two patients who required intraoperative rescue analgesia (Wilcoxon-Mann-Whitney test: P < 0.05). These were also the only two patients who received one intra- and one postoperative dose of opioid each (7.6%). Conclusion: US-guided rectus sheath block seems to be a simple and quick method for the provision of intra- and postoperative analgesia in infants undergoing conventional HPS surgery. [ABSTRACT FROM AUTHOR]

Abstract: Context: Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients. Objectives: The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients. Methods: The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain. Results: Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain. Conclusion: Breakthrough cancer pain is an extremely heterogeneous condition. [Copyright &y& Elsevier]

Highlights: [•] This study aimed to predict responders to treatment with the capsaicin 8% patch. [•] Responders had lower baseline pressure pain thresholds in affected vs control areas. [•] Non-responders had worse allodynia at baseline than responders. [•] After therapy, all patients achieved reductions in the size of the painful area. [Copyright &y& Elsevier]

Objective: The lumbar sympathetic trunk's (LST) distance to two anatomical landmarks, the costal process and medial margin of the psoas muscle, was assessed due to its use as landmarks for lumbar sympathetic blocks: the costal process for fluoroscopic guided techniques and the psoas major for CT- and MRI-guided techniques. Based on the measurements, we evaluate the trunk's visibility in MR and CT images for accurate positioning of the needle. Methods: A total of 54 cadavers embalmed with Thiel's method were investigated. The LST's distances to the psoas major's medial margin and to the base of the lumbar vertebrae's costal process were measured on the levels L2/3, L3/4 and L4/5. The measurements were compared to MR and CT images of 20 anonymous patients to identify the LST. Results: LST's mean distance to the psoas major was 0.3 mm at L2/3, 3.1 mm at L3/4 and 4.6 mm at L4/5. The mean distance to the costal process was 31 mm at L2/3, 34 mm at L3/4 and 32.6 mm at L4/5. In both MR and CT imaging, a structure could be determined as the LST correlating to the measurements with decreasing possible identification from cephalad to caudad levels. Conclusions: The costal process is a usable landmark for fluoroscopic guidance and the psoas major for CT- and MRI-guided techniques. The LST is clearly visible in MR and CT images, which gives both techniques a decisive advantage over fluoroscopy concerning the block of the LST due to a visible target. [ABSTRACT FROM AUTHOR]

Background: In this study, we analyze the impact of the choice of either the left or right brachiocephalic vein (BCV) on the cannulation success when using the ultrasound-guided supraclavicular in-plane technique approach to the longitudinally viewed BCV in infants. Methods: The central vascular protocols of 183 infants were reviewed retrospectively. Results: The weight ranged from 0.7 to 10 kg. Central venous catheter placement was eventually successful in 98.9%. In 141 patients (82.9%), the left BCV was successfully punctured on the first attempt, in 23 patients (13.5%) after 2 and in 6 patients (3.5%) after 3 attempts. The right BCV was successfully punctured on the first attempt in five patients (38.4%), in three patients (15.3%) after two and in five patients (38.4%) after three attempts, respectively. Significantly more puncture attempts were required for the right BCV (chi-square analysis: P < 0.01). There was also a significant improvement of the success rate over the time course of the case series (Jonckheere-test: P < 0.01). Conclusion: It seems to be easier to cannulate the left BCV than the right BCV when using this ultrasound-guided supraclavicular strict in-plane technique. Gaining experience with this method seems to improve the cannulation success. [ABSTRACT FROM AUTHOR]

Activation of opioid receptors on peripheral sensory nerve terminals by opioid peptides that are produced and released from immune cells can result in inhibition of inflammatory pain. This study tests the hypothesis that postoperative pain is attenuated endogenously through a local sympathetic neurotransmitter-activated release of opioids in patients undergoing knee surgery. We examined the expression of opioid peptides and adrenergic receptors in cells infiltrating inflamed synovial tissue and we hypothesized that intra-articular (i.a.) administration of the adrenergic receptor antagonist labetalol will increase postoperative analgesic consumption and/or pain intensity in these patients. In a double-blind, randomized manner, 75 patients undergoing therapeutic knee arthroscopy received i.a. placebo (20 ml saline) or labetalol (2.5 or 5 mg in 20 ml saline) at the end of surgery. Postoperative pain intensity was assessed by visual analog and verbal rating scales at rest and on exertion, and by the consumption of morphine via patient-controlled analgesia. Synovial biopsies were taken during the operation for double-immunofluorescence confocal microscopy studies. Alpha- and beta-adrenergic receptors were co-expressed in opioid peptide-containing cells. No significant difference was seen in pain scores, but patients receiving 2.5 mg labetalol requested significantly higher amounts of morphine. These findings are consistent with the notion that surgical stress induces sympathetically activated release of endogenous opioids from inflammatory cells and subsequent analgesia via activation of peripheral opioid receptors. [ABSTRACT FROM AUTHOR]

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. [ABSTRACT FROM AUTHOR]

Stimulation of primary afferent neurons offers a new approach for the control of localized chronic pain. We describe the results with a new neurostimulation technique, subcutaneous target stimulation (STS), for the treatment of chronic focal noncancer pain. STS applies permanent electrical stimulation directly at the painful area via a percutaneous-placed subcutaneous lead. We reported the clinical outcomes of 111 patients with focal chronic, noncancer pain treated with STS in this first nationwide, multicenter retrospective analysis. The indications for STS were low back pain ( n = 29) and failed back surgery syndrome (back pain with leg pain) ( n = 37), cervical neck pain ( n = 15), and postherpetic neuralgia ( n = 12). Pain intensity was measured on a numerical rating scale (NRS) before and after implantation. Data on analgesic medication, stimulation systems, position, and type of leads and complications were obtained from the patients' records. After implantation, the mean pain intensity improved by more than 50% (mean NRS reduction from 8.2 to 4.0) in the entire patient group ( P = 0.0009). This was accompanied by a sustained reduction in demand for analgesics. In all the patients, the STS leads were positioned directly at the site of maximum pain. Lead dislocation occurred in 14 patients (13%), infections in 7 (6%), and in 6 cases (5%), lead fractures were observed. The retrospective data analysis revealed that STS effectively provided pain relief in patients suffering from refractory focal chronic noncancer pain and that STS is an alternative treatment option. Prospective controlled studies are required to confirm these retrospective findings. This article presents a new minimally invasive technique for therapy-resistant focal pain. [ABSTRACT FROM AUTHOR]

▪ Abstract 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The “baby-boomers” in their 60s and 70s are “baby zoomers”; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities—including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia—and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation—fentanyl and buprenorphine—fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2. The use of opioids in noncancer-related pain: Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying... [ABSTRACT FROM AUTHOR]

Background: Behavioral disturbance in children following sevoflurane anesthesia is a relatively frequent event. The aim of this study was to evaluate whether a higher dose of preoperatively administered rectal midazolam compared with a lower would alleviate this phenomenon. Furthermore the impact of these two doses of midazolam on sedation at induction of anesthesia was compared. Methods: A total of 115 children presenting for minor surgery under anesthesia were included in the study. The children were randomized to receive rectally either 1 mg·kg−1 midazolam (group H) or 0.5 mg·kg−1 midazolam (group L). General anesthesia was induced with propofol or sevoflurane and maintained with 1.5% sevoflurane in the inspiratory limb. Prior to the start of surgery a regional block was performed to ensure adequate pain relief. Behavior on emergence was assessed using a three point scale. In case of severe agitation propofol was administered IV. Results: The children in group H were significantly better sedated preoperatively ( P < 0.01). There was no significant difference in emergence behavior: 42.1% of children in group H compared with 36.2% of children in group L exhibited severe agitation requiring sedation with propofol ( P = 0.37). However, regardless of the preoperative dose of midazolam more children under the age of 36 months (61.4%) were severely distressed at emergence compared with older children (16.7%) ( P < 0.01). Conclusions: A higher dose of 1 mg·kg−1 rectal midazolam results in much better sedated children on induction of anesthesia than 0.5 mg·kg−1. This, however, does not result in a reduced incidence of emergence delirium after sevoflurane anesthesia. Regardless of the premedication negative behavioral changes occur more frequently in children younger than 3 years of age. [ABSTRACT FROM AUTHOR]

The aim of our study was to compare postoperative analgesic efficacy, analgesic duration and motor blockade of levobupivacaine, ropivacaine and bupivacaine administered caudally in equal concentrations to children undergoing elective minor surgery.In the study, 182 children, aged 1–7 years, undergoing either inguinal hernia repair or orchidopexy, were randomly allocated to one of the three groups. They received via a caudal extradural either 1 ml·kg−1 levobupivacaine 0.2% (Group L) or 1 ml·kg−1 ropivacaine 0.2% (Group R) or 1 ml·kg−1 bupivacaine 0.2% (Group B).No statistically significant difference was noted in age, weight, duration of the operation or level of the caudal block between the groups. The onset of analgesia was significantly later after levobupivacaine. Postoperative pain scoring evaluated with Children's and Infant's Postoperative Pain Scale observational scale showed no statistical difference between groups. Median postoperative analgesia was 5.75 h (SEMed:± 0.65) in Group L, 5.7 h (SEMed:± 0.8) in Group R and 5.35 h (SEMed:± 1.3) in Group B the difference being statistically nonsignificant.The degree of motor block was significantly less after ropivacaine and levobupivacaine during the first 2 h postoperatively. [ABSTRACT FROM AUTHOR]

Severe limb ischemia after arterial catheterization in neonates and premature infants is a well-recognized problem. The usual treatment of ischemic injuries includes removal of the catheter and elevation of the effected limb. If unsuccessful, tissue necrosis and loss may follow. We report the case of a 700 g infant with severe distal forearm ischemia after right radial and ulnar artery catheterization. Immediate removal of the arterial line did not improve ischemia. Thirty-six hours later a brachial plexus block via the axillary approach with 0.5 ml bupivacaine 0.125% was performed resulting in rapid improvement, restricting ischemia eventually to fingers II–V as well as the distal part of the thumb. Brachial plexus blockade and active vasodilatation in tiny neonates after severe local ischemia are discussed. [ABSTRACT FROM AUTHOR]

Adequate pain therapy is an important aspect in the treatment of the elderly patient with rheumatoid disease. Problems with traditional NSAIDs include potentially serious gastrointestinal, cardiovascular and renal adverse effects, especially in the elderly. In addition, the selective cyclo-oxygenase-2 inhibitors have been associated with renal and cardiovascular adverse effects which may limit their use in the elderly with renal or cardiovascular disease. Opioids provide a treatment option for the management of pain in elderly patients with rheumatoid disease in whom pain control under standard management is poor; however, various therapeutic difficulties are encountered in the heterogenous elderly population (increased risk of adverse effects, multimorbidity, and polypharmacy). Lower initial opioid dosage, prolonged dosage intervals and slower dosage titrations are advisable because of altered pharmacokinetics and pharmacodynamics. Kidney function should be tightly monitored and a timely use of laxatives is to be encouraged. Randomised clinical studies of opioids in musculoskeletal pain (e.g. osteoarthritis) have increasingly extended the scientific basis for their use. However, no randomised controlled clinical trials have examined the efficacy and the benefit/risk ratio of opioids in rheumatoid arthritis. Opioids also demonstrate an analgesic effect following local peripheral application. This opens the way to new therapeutic options in the future through the development of systemic peripherally selective opioids without CNS adverse effects. [ABSTRACT FROM AUTHOR]

Clonidine ((2-[2,6-dichlorophenyl]amino)-2-imidazoline) preferentially stimulates central α2-adrenoceptors, which leads to inhibition of sympathetic tone, resulting in a lowering of arterial pressure and of heart rate. Additionally, many other desirable and undesirable effects are described, including analgesia, sedation and withdrawal reactions, which consist of a sudden rise in arterial pressure, nervousness, agitation and increased heart rate.The present study has the goal to develop a simple and effective method for the analysis of trace amounts of clonidine in human blood serum. Special emphasis is necessary to make application of electron impact ionization and separation of the analyte fragments in a quadruple mass analyzer suitable. The procedure comprises solid phase extraction followed by formation of the pentafluorobenzyl derivative. Further purification is achieved by phase transfer extraction into an acidic aqueous solution succeeded by re-extraction into dichloromethane. After solvent exchange, an aliquot is injected into the gas chromatograph equipped with a DB5 MS capillary column and a mass spectrometric detector. Chromatograms are recorded in single ion monitoring mode. Quantification is accomplished by internal standardization with moxonidine [4-chloro-5-(2-imidazolin-2-yl-amino)-6-methoxy-2-methylpyridine]. [Copyright &y& Elsevier]

A neonate with chromosomal 9 abnormality and omphalocele received a lumbar epidural catheter after laparotomy. Several attempts were needed to establish this catheter. Bleeding occurred from the operative wound after surgery. Using an epidural infusion with ropivacaine 0.1% for 48 h postoperative pain relief was sufficient. Four days after epidural catheter removal, dysfunction of the sacral parasympathetic nerves was noted. Motor and sensor function of the lower limbs were unaffected. Magnetic resonance imaging showed a localized intraspinal haematoma in the lower lumbar region. [ABSTRACT FROM AUTHOR]

SummaryThe case of a 680 g premature baby who developed massive spontaneous liver haemorrhage during laparotomy for necrotizing enterocolitis is reported. The infant survived due to rapid and massive fluid administration, including transfusion of large volumes of blood and blood products, in combination with high dose inotropic support and the surgical use of packing with thrombostatic sponges. Good venous access, including two central venous lines, turned out to be very useful. [ABSTRACT FROM AUTHOR]

The article examines the use of the Nitinol Mandril wire-guide for subclavian vein cannulation in two very small preterm infants. The author implies that cannulation of the subclavian, internal jugular or brachiocephalic vein is a challenging and also dangerous procedure, especially in infants. The report also demonstrates that successful advancement of a guide-wire into the subclavian or internal jugular vein in very small neonates can be more easily achieved by the use of tyhe Nitinol Mandril wire-guide with its soft angled platinum coil tip.

Annually, thousands of air travellers visit high altitude destinations to enjoy hiking tours to attractions in surrounding areas. However, many of them are not adequately trained, not sufficiently acclimatized and/or may suffer from pre-existing diseases. To prevent adverse health effects and unpleasant experiences at high altitude, simple submaximal exercise testing at low altitude for the prediction of exercise tolerance at high altitude would be helpful. Therefore, 40 healthy males and females performed submaximal exercise tests at low (600 m) and high altitude (3500 m). We demonstrate that exercise tolerance during acute exposure to high altitude can be predicted by the individual heart rate response to submaximal exercise assessed at low altitude. [ABSTRACT FROM AUTHOR]