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Treatment of postoperative pain after ear, nose and throat (ENT) cancer surgery is mainly morphine administration. Additional systemic lidocaine has shown promising results in some surgical procedures.The main objective was to evaluate morphine consumption in the first 48 postoperative hours after intra-operative lidocaine infusion during major ENT cancer surgery.A randomised, double-blind, placebo-controlled trial.Bicentric study including a university hospital and a major cancer centre, conducted from December 2016 to December 2019.A total of 144 patients undergoing major ENT cancer surgery were included.The patients were randomly assigned to receive intravenous lidocaine or placebo during surgery and in the recovery room.Endpoints were postoperative morphine consumption in the first 24 and 48 h postoperatively, intra-operative remifentanil consumption, adverse events occurrence and assessment 3 to 6 months after surgery with the McGill pain questionnaire.A total of 118 patients were included (lidocaine n = 57; placebo n = 61, 26 patients were excluded). There was no significant difference in morphine consumption during the first 48 postoperative hours in the lidocaine group compared with the placebo group with a median [IQR] of 0.60 [0.30 to 1.03] mg kg -1 vs. 0.57 [0.37 to 0.96] mg kg -1 , total dose 44 [21 to 73.3] mg vs. 38 [23.3 to 56.5] mg, P = 0.92.There was no significant difference between the two groups in any of the other endpoints, including at follow up 3 to 6 months after surgery.Intravenous lidocaine in ENT cancer surgery did not show any additional analgesic or morphine-sparing effect 48 h after surgery. Three to six months after surgery, there was no significant difference in pain scores or consumption of analgesics. Patients treated pre-operatively with opioids were not evaluated in the study.Clinicaltrials.gov identifier: NCT02894710 and EUDRACT number 2015-005799-90.

SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019.To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France.A retrospective study.Six ICUs in a single institution in Lyon, France.Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021.Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model.COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement.After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

BACKGROUND Orthotopic liver transplantation is associated with a risk of bleeding. Coagulation in cirrhotic patients is difficult to assess with standard coagulation tests because of rebalanced coagulation. This can be better assessed by thromboelastometry which can detect coagulation impairments more specifically in such patients. OBJECTIVES Our first objective was to compare the number of units of blood products transfused during liver transplantation when using an algorithm based on standard coagulation tests or a thromboelastometry-guided transfusion algorithm. DESIGN Randomised controlled trial. SETTING Single-centre tertiary care hospital in France, from December 2014 to August 2016. PARTICIPANTS A total of 81 adult patients undergoing orthotopic liver transplantation were studied. Patients were excluded if they had congenital coagulopathies. INTERVENTION Transfusion management during liver transplantation was guided either by a standard coagulation test algorithm or by a thromboelastometry-guided algorithm. Transfusion, treatments and postoperative outcomes were compared between groups. MAIN OUTCOME MEASURES Total number of transfused blood product units during the operative period (1 U is one pack of red blood cells (RBCs), fresh frozen plasma (FFP) or platelets). RESULTS Median [interquartile range] intra-operative transfusion requirement was reduced in the thromboelastometry group (3 [2 to 4] vs. 7 [4 to 10] U, P = 0.005). FFP and tranexamic acid were administered less frequently in the thromboelastometry group (respectively 15 vs. 46.3%, P = 0.002 and 27.5 vs. 58.5%, P = 0.005), whereas fibrinogen was more often infused in the thromboelastometry group (72.5 vs. 29.3%, P

Background Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. Objectives To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics. Design A single centre prospective study. Setting University Hospital, Paris, France, from 2 January 2007 to 15 November 2011. Patients A total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction. Interventions Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h. Main outcome measures The dose of morphine required to achieve pain relief and the influence of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements. Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events. Results A total of 404 patients completed the study to final analysis. The mean ± SD morphine dose to achieve pain relief was 15.8 ± 8.8 mg in the PACU and 22.7 ± 18.6 mg during patient-controlled intravenous administration. Morphine-related adverse events were observed in 37%. There was no relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of the model was poor (R = 0.04) CONCLUSION: No major relationship has been demonstrated between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period. Trial registration NCT00822549 (www.clinicaltrials.gov).

Hepatic surgery is a major abdominal surgery. Epidural analgesia may decrease the incidence of postoperative morbidities. Hemostatic disorders frequently occur after hepatic resection. Insertion or withdrawal (whether accidental or not) of an epidural catheter during coagulopathic state may cause an epidural hematoma. The aim of the study is to determine the incidence of coagulopathy after hepatectomy, interfering with epidural catheter removal, and to identify the risk factors related to coagulopathy.We performed a retrospective review of a prospective, multicenter, observational database including patients over 18 years old with a history of liver resection. Main collected data were the following: age, preexisting cirrhosis, Child-Pugh class, preoperative and postoperative coagulation profiles, extent of liver resection, blood loss, blood products transfused during surgery. International normalized ratio (INR) ≥1.5 and/or platelet count80,000/mm defined coagulopathy according to the neuraxial anesthesia guidelines. A logistic regression analysis was performed to assess the association between selected factors and a coagulopathic state after hepatic resection.One thousand three hundred seventy-one patients were assessed. Seven hundred fifty-nine patients had data available about postoperative coagulopathy, which was observed in 53.5% [95% confidence interval, 50.0-57.1]. Maximum derangement in INR occurred on the first postoperative day, and platelet count reached a trough peak on postoperative days 2 and 3. In the multivariable analysis, preexisting hepatic cirrhosis (odds ratio [OR] = 2.49 [1.38-4.51]; P = .003), preoperative INR ≥1.3 (OR = 2.39 [1.10-5.17]; P = .027), preoperative platelet count150 G/L (OR = 3.03 [1.77-5.20]; P = .004), major hepatectomy (OR = 2.96 [2.07-4.23]; P.001), and estimated intraoperative blood loss ≥1000 mL (OR = 1.85 [1.08-3.18]; P = .025) were associated with postoperative coagulopathy.Coagulopathy is frequent (53.5% [95% confidence interval, 50.0-57.1]) after liver resection. Epidural analgesia seems safe in patients undergoing minor hepatic resection without preexisting hepatic cirrhosis, showing a normal preoperative INR and platelet count.

Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjogren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.

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Background The evaluation of pain intensity during the immediate postoperative period is a key factor for pain management. However, this evaluation may be difficult in some circumstances. The pupillary dilatation reflex (PDR) has been successfully used to assess the analgesic component of a balanced anesthetic regimen. We hypothesized that PDR could be a reliable index of pain intensity and could guide morphine administration in the immediate postoperative period. Methods One hundred patients scheduled to undergo general surgery were included in this prospective observational study. Pain intensity was assessed by using a simple five-item verbal rating scale (VRS). After patients awoke from general anesthesia, those experiencing mild or more severe pain (VRS more than 1) received intravenous morphine titration. Before and after intravenous morphine titration, the PDR induced by a standardized noxious stimulus was measured with a portable pupillometer. A receiver-operating curve was built to estimate the accuracy of PDR in objectively detecting patients requiring morphine titration. Results are given as median (95% CI). Results On the initial evaluation, a correlation was found between VRS and PDR (ρ = 0.88 [0.83-0.92], P < 0.0001). In the 39 patients that had a VRS more than 1, PDR before and after morphine titration was respectively 35% (31-43) versus 12% (10-14); P < 0.0001. The PDR threshold value corresponding to the highest accuracy to have VRS more than 1 was 23%, with 91% and 94% sensitivity and specificity, respectively. Conclusion In the immediate postoperative period, the PDR is significantly correlated with the VRS. The pupillometer could be a valuable tool to guide morphine administration in the immediate postoperative period.

Epidural clonidine has been proposed as an adjunct for anaesthetic mixtures during labour. Administered as a bolus, clonidine may have side effects such as sedation and hypotension; its continuous infusion could be attractive in this respect. We, therefore, conducted a randomized, double-blind trial using patient-controlled epidural analgesia with a background infusion using a low dose of clonidine during labour.A total of 128 healthy parturients in active labour received a patient-controlled epidural analgesia solution of 0.0625% levobupivacaine and sufentanil 0.25 microg ml(-1) with or without clonidine 2 microg ml(-1). Ninety-five parturients were analysed. The pain score over time was evaluated as well as drug volume utilization; supplementation bolus and side effects were recorded. The primary endpoint was maternal satisfaction [ClinicalTrials.gov Identifier (NCT00437996)].Three patients in the control group failed to achieve satisfactory epidural analgesia owing to a technical issue. Although the primary endpoint was not statistically significant, analgesia was more pronounced and obtained earlier in the clonidine group. The area under the curve for the visual analogue pain score was significantly lower in the clonidine group. In this group, hourly doses of levobupivacaine and sufentanil were reduced (13.9 +/- 4.3 vs. 16.3 ml +/- 4.0; P = 0.005) as well as rescue supplementation and pruritus incidence (18 vs. 46%; P = 0.004). Maternal blood pressure was significantly lower, over time, in the clonidine group but remained within the normal range. Sedation was similar in both groups (4.3 vs. 2.0%; not significant).The addition of clonidine to epidural levobupivacaine and sufentanil for patient-controlled epidural analgesia in labour improved analgesia, reduced the supplementation rate and reduced pruritus without improvement in maternal satisfaction. Blood pressure was significantly lower in the clonidine group over time but without clinical consequence.

I.v. morphine titration (IMT) is widely used in the postanesthesia care unit to achieve pain relief. Numerous factors contribute to variability in postoperative pain or morphine consumption. We analyzed prospectively the pre- and intraoperative predictive factors of severe postoperative pain defined as a dose of IMT0.15 mg/kg or a failure of IMT.We assessed the role of preoperative information about pain, medical treatments, and intraoperative events and their role on postoperative pain. After IMT, patients were divided into two groups: severe pain (SP) and nonsevere pain. Data are expressed as mean +/- SD.Three hundred forty-two patients were included in the study: 200 (58%) in the nonsevere pain group and 142 (42%) in the SP group. Using a univariate analysis, there was no significant difference between groups related to medical or surgical history except for more frequent preoperative treatments in the SP group (P0.05). Duration of the surgical procedure and anesthesia were longer in the SP group (P0.001). The dose of sufentanil and visual analog scale scores before and at the end of IMT were higher in the SP group (P0.001). Using a multivariate analysis, a high dose of intraoperative opioid (sufentanil dose0.6 microg/kg) (Odds ratio = 2.68, P0.001), a general anesthetic procedure (Odd ratio = 3.96, P = 0.03), and the use of preoperative analgesic drugs (Odds ratio = 1.91, P0.01) were independent factors associated with severe postoperative pain.A higher intraoperative dose of sufentanil, general anesthesia, and preoperative treatment with analgesics were significantly associated with severe postoperative pain.

Background and objectiveMajor gynaecological abdominal surgery is associated with moderate to severe postoperative pain, hyperalgesia and the need for multimodal analgesia to reduce high morphine consumption. A low-dose ketamine regimen appears to prevent postoperative hyperalgesia. We examined the potential beneficial effect of ketamine on postoperative pain management and cognitive function.MethodsNinety patients were included in this double-blind, randomized, placebo-controlled study to test the efficacy and adverse effects of ketamine (as an intraoperative bolus of 0.15 mg kg−1, followed postoperatively by ketamine 0.5 mg per morphine 1 mg in a patient-controlled analgesia device). All patients received additionally ketoprofen. The main end-point was morphine consumption over the first 24 h. Secondary efficacy and safety end-points were morphine consumption during the titration period and during the patient-controlled analgesia period (48 h), the number of morphine-related adverse effects and the results of psychometric tests.ResultsKetamine, in combination with morphine and ketoprofen, did not improve postoperative pain scales and did not reduce morphine consumption and the incidence of morphine-related adverse effects. Ketamine did not modify mood, cognitive and memory functioning.ConclusionAdding a low dose of ketamine to an efficacious multimodal analgesic regimen did not improve analgesia after gynaecological surgery. Although this combination appears to be safe, the lack of benefit suggests that a low dose of ketamine should not be used for routine care.

Background Sex-related differences in the perception of pain and susceptibility to opioids remain a matter of debate. Intravenous morphine titration used to obtain pain relief in the immediate postoperative period is a unique clinical model for assessing the effect of sex on reported pain. Because of the wide variation in dose requirements for pain management, the authors conducted a prospective study in a large population and also assessed the effect of aging. Methods Intravenous morphine titration was administered as a bolus of 2 (body weight 60 kg) during the immediate postoperative period. The interval between each bolus was 5 min. The visual analog pain scale (VAS) threshold required to administer morphine was 30, and pain relief was defined as a VAS score of 30 or less. Data are expressed as mean +/- SD. Results Data from 4,317 patients were analyzed; 54% of the patients were male, and 46% were female. The mean morphine dose required to obtain pain relief was 11.9 +/- 6.8 mg or 0.173 +/- 0.103 mg/kg. Women had a higher initial VAS score (74 +/- 19 vs. 71 +/- 19; P < 0.001) and required a greater dose of morphine (0.183 +/- 0.111 vs. 0.165 +/- 0.095 mg/kg; P < 0.001). In contrast, no significant difference was noted in elderly (aged > 75 yr) patients (0.163 +/- 0.083 vs. 0.157 +/- 0.085 mg/kg). Conclusion Women experienced more severe postoperative pain and required a greater dose (+11%) of morphine than men in the immediate postoperative period. This sex-related difference disappeared in elderly patients.

Background It has been suggested that the dose of intravenous morphine used during postoperative titration is not modified by aging. The authors therefore studied morphine requirements in patients undergoing total hip replacement. Methods Intravenous morphine titration was administered as boluses, then subcutaneous morphine was administered every 4 h over 24 h. Pain was assessed by use of the visual analog scale (0 to 100), and the threshold required to administer morphine was 30. Young and elderly (> or =70 yr old) patients were compared. Data are mean +/- SD or odds ratio (OR) [95% CI]. Results Two hundred twenty-four patients (68%) were young and 105 (32%) were elderly. The initial visual analog scale was not significantly different between groups. The dose of intravenous morphine in the postanesthesia care unit was not significantly different between young and elderly patients (0.15 +/- 0.11 vs. 0.14 +/- 0.10 mg/kg, P = NS), in contrast to the dose of subcutaneous morphine (0.18 +/- 0.18 vs. 0.11 +/- 0.11 mg/kg, P < 0.001) in the ward. Only severe pain (visual analog scale of 70 or greater; OR, 10.5 [4.5-24.8]) was significantly associated with a high dose (greater than 0.15 mg/kg) of intravenous morphine, whereas severe pain (OR, 2.5 [1.6-4.0]), age less than 60 yr (OR, 2.3 [1.4-3.8]), and absence of a nonsteroidal antiinflammatory drug (OR, 1.9 [1.2-3.1]) were significantly associated with a high dose (greater than 0.12 mg/kg) of subcutaneous morphine. Conclusions The dose of intravenous morphine during titration is not modified in elderly patients, in contrast to the dose administered subcutaneously over a prolonged period.

Background Although intravenous morphine titration is widely used to obtain rapid and complete postoperative pain relief, the relationship between measurement of pain and morphine requirements varies, and the evolution of pain during titration is poorly understood. Methods Intravenous morphine titration was administered as a bolus of 2 (body weight < or = 60 kg) or 3 mg (body weight > 60 kg) during the immediate postoperative period in the PACU. The interval between each bolus was 5 min. The visual analog scale (VAS) score threshold required to administer morphine was 30, and pain relief was defined as a VAS score of 30 or less. Results Data from 3,045 patients were analyzed. The mean initial VAS score was 73 +/- 19 (mean +/- SD), and the mean morphine dose required to obtain pain relief was 0.17 +/- 0.10 mg/kg, i.e., a median of four boluses (range, 1-20). When patients were grouped according to several classes of initial VAS score (31-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-100), it seemed that the relationship between VAS score and morphine requirements was a sigmoid curve. A VAS score of 70 or greater predicted the need for a high (>0.15 mg/kg) morphine dose (sensitivity, 0.77; specificity, 0.54). During the pain relief process, the relationship between VAS score and time was depicted by a sigmoid curve. Conclusion A VAS score of 70 or greater should be considered indicative of severe pain. The relationship between the initial VAS score and morphine requirements is not linear, and the evolution of the VAS score during the pain relief process is described by a sigmoid curve.

Background Intravenous morphine titration is used to obtain rapid and complete postoperative pain relief. Whether this titration can be safely administered in the elderly patients remains a matter for debate. Methods Intravenous morphine titration was administered as a bolus of 2 (body weight < or = 60 kg) or 3 (body weight > 60 kg) mg. The interval between each bolus was 5 min. There was no limitation in the number of boluses given until pain relief or severe adverse effect occurred. The visual analog scale threshold required to administer morphine was 30 mm, and pain relief was defined as a visual analog scale score of 30 mm or less. Patients were divided into two groups: young and elderly (age > or = 70 yr) patients. Data were expressed as mean +/- SD. Results Eight hundred seventy-five patients (83%) were young and 175 patients (17%) were elderly. At the end of morphine titration, the visual analog scale score and the number of patients with pain relief were not significantly different between groups. The total dose of morphine per kilograms of body weight administered was not significantly different between groups (0.15 +/- 0.10 vs. 0.14 +/- 0.09 mg/kg, not significant). No significant differences were observed in the incidence of morphine-related adverse effects (13 vs. 14%, not significant), the number of sedated patients (60 vs. 60%, not significant), and the number of patients whose titration had to be stopped (2 vs. 2%, not significant). Conclusion Intravenous morphine titration can be safely administered to elderly patients. Because titration is adapted to individual pain, the same protocol can be applied to young and elderly patients.