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We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, PaO2 = 95–105 mm Hg) or hypoxemia (group HypoxRes, PaO2 = 35–40 mm Hg). Animals not subjected to shock constituted the sham group (PaO2 = 95–105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy.Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit.Thirty-one New Zealand white rabbits weighting 3.1-3.4 kgAnesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40 mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (n=11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate.Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate.Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.

A comparison of outcomes between different modes of head-injury treatment in the elderly has important bearing on questions of cost-effectiveness and medical ethics. Here, we have examined rates of mortality in elderly head-trauma victims to determine whether it is valid to differentiate an "edge" age group of younger elderly patients, 65-74 years of age, from older elderly patients, considering possible benefit from intensive treatment and surgical intervention. We collected data from 1926 cases of head trauma and separated them into three age groups: 14-64 years, 65-74 years, and 75 years or older. We then compared these groups with respect to cause of injury, severity of injury, and whether or not treatment included either admission to an Intensive Care Unit (ICU) or surgical intervention. We found that road traffic accidents were the major cause of head injury in the younger age group, whereas in the elderly falls predominated. Mortality was higher in the elderly in all the head injury severity subgroups. Young subjects with a Glasgow Coma Scale (GCS) score of less than or equal to 8 tended to benefit from ICU treatment whereas patients 75 and over did not, regardless of their severity of injury. For these patients who were in the 65-74 age group, the data suggested that some benefit was likely. Patients 75 and older were significantly less likely to survive surgical intervention than younger patients. We conclude that it is valid to treat patients in the age group 65-74 years as a separate group from those patients 75 and older. Patients in this younger subset of the elderly may benefit from ICU treatment or surgical intervention. However, the patients in our older subset of elderly patients clearly did not, and they had a significantly higher risk of surgical mortality.

We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes.Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups.The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion.Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome.

Background and purpose: Reactive oxygen species contribute to membrane lipid peroxidation and neuronal death and have been implicated in anoxic encephalopathy. We tested whether hypoxemic reperfusion (HR) after global cerebral ischemia would improve neurological recovery. Methods: Two groups of pigs (n=11 in each group) were subjected to a model of a 10-min global cerebral and systemic ischemia to compare the effect of hypoxemic reperfusion (group HR) with the classical hyperoxemic control (group C). A third group not subjected to ischemia served as control to the control group (n=6, group CC), but received hyperoxygenation at the respective period of reperfusion. The outcome was evaluated by means of neurological assessment and the extent of lipid peroxidation measuring the plasma malonaldehyde (MDA) together with hydroxyalkenals (HALK). Results: Animals of group HR exhibited a significantly superior neurological outcome compared with those of group C at all three consecutive assessments after reperfusion (post-resuscitation P=0.006, at 8 h P=0.003, and at 24 h P=0.007). The levels of MDA and HALK are lower in the HR group than in group C (P=0.029). Additionally, in the CC group these molecules increased significantly early at hyperoxygenation (P=0.02). A faster lactate metabolism in the HR group was observed during reperfusion, though non-significant. Conclusions: Hypoxemic reperfusion during resuscitation from a severe global ischemic cerebral insult improves the neurological outcome compared with classic hyperoxemic reperfusion. This is additionally confirmed by the decreased production of the molecules of lipid peroxidation. In the absence of preceding ischemia, these molecules may increase by simple over-oxygenation.

To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims.Prospective, randomized, double-blind, placebo-controlled study.A 20-bed university intensive care unit.Thirty-nine trauma patients with injury severity scores (ISSs) of 16-50.Penicillin was given at the time of admission and continued at least until day 4. Twenty-one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p = .02), at the time of admission. Blood was collected on days 1, 4, and 7.Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37 degrees C (98.6 degrees F) and 40 degrees C (104.0 degrees F) at the time of admission and during the course of IVIG administration. Controlling for ISS, IVIG-treated patients had fewer pneumonias (p = .003) and total non-catheter-related infections (p = .04). Catheter-related infections (p = .76), length of stay in the intensive care unit, antibiotic days, and infection-related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p.000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p.000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40 degrees C (104.0 degrees F) compared with 37 degrees C (98.6 degrees F) (p.0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p.01) and non-catheter-related infections (p = .06 for day 1; p.01 for days 4 and 7).Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.

In order to explore whether an organ-specific pattern in cytokine and lactate concentrations exists in patients with multiple organ failure (MOF), we measured the cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary capillaries, and peripheral veins of 10 patients with MOF with hepatic involvement (MOF-HI), eight patients with MOF and adult respiratory distress syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional patients participated in a study of arteriovenous pulmonary concentration gradients of these substances. For statistical analysis, nonparametric tests and analysis of variance (ANOVA) were used. The regional concentrations of these substances exhibited a different pattern in the two MOF groups. In the MOF-HI group, mean +/- SD cytokines IL-1beta and IL-6 (pg/ml) were respectively 216 +/- 100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204 in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and 235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF-alpha levels also exhibited the same pattern. The mean +/- SD corresponding levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3, and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0 +/- 0.2, respectively. The differences in the levels of all substances between the liver and lungs in the two MOF groups were statistically significant (p0.003). In the study of transpulmonary gradients it was shown that the levels of cytokine and lactate were lower in arterial blood than in mixed venous blood in MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this study, we found that in MOF, cytokines and lactate are secreted from the most severely affected organs.

Systemic infection with Aspergillus fumigatus is an opportunistic disease that affects mainly immunocompromised hosts and is associated with a high mortality rate. We report a case of A. fumigatus endocarditis after an episode of thrombotic thrombocytopenic purpura. Diagnosis was established after sudden rupture of posterior papillary muscle of the normal native mitral valve. Soon after mitral valve replacement, Aspergillus endocarditis recurred, associated with multiple peripheral emboli, which necessitated a second operation.

Introduction A case of fasciitis and septic shock complicating retrocecal appendicitis is presented. Case report A 52-year-old man presented to the Emergency Department with lumbar pain, fever of recent onset and subsequently developed septic shock attributed to fasciitis of abdominal, flank and groin region. On intensive care unit, he was managed with broad-spectrum intravenous antibiotics and surgical debridement. An abdominal computed tomography scan confirmed the findings of fasciitis and was negative for intra-abdominal pathology. In the following days, an enterocutaneous fistula with foul smelling fluid was noted. A new surgical exploration revealed the presence of a ruptured retrocecal appendix, and right hemicolectomy was performed. The postoperative period was long but uneventful. Conclusion Retrocecal appendicitis can rarely be presented as deteriorating cellulitis—fasciitis in the right abdominal, flank or groin region, with or without abdominal symptoms.

AIM: To investigate factors predicting failure of percutaneous endoscopic gastrostomy (PEG) to eliminate gastroesophageal reflux (GER). METHODS: Twenty-nine consecutive mechanically ventilated patients were investigated. Patients were evaluated for GER by pH-metry pre-PEG and on the 7th post-PEG day. Endoscopic and histologic evidence of reflux esophagitis was also carried out. A beneficial response to PEG was considered when pH-metry on the 7th post-PEG day showed that GER was below 4%. RESULTS: Seventeen patients responded (RESP group) and 12 did not respond (N-RESP) to PEG. The mean age, sex, weight and APACHE Ⅱ score were similar in both groups. GER (%) values were similar in both groups at baseline, but were significantly reduced in the RESP group compared with the N-RESP group on the 7th post-PEG day [2.5 (0.6-3.8) vs 8.1 (7.4-9.2, P < 0.001)]. Reflux esophagitis and the gastroesopha geal flap valve (GEFV) grading differed significantly between the two groups (P = 0.031 and P = 0.020, respectively). Histology revealed no significant differ ences between the two groups. CONCLUSION: Endoscopic grading of GEFV and the presence of severe reflux esophagitis are predisposing factors for failure of PEG to reduce GER in mechanically ventilated patients.

The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFalpha were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.

We report the use of endoscopic techniques for successful diagnosis in a case of atypical esophageal tuberculosis. Tuberculosis of the esophagus is an unusual presentation of this disease, having been estimated to occur in 0.15% of the people who die of tuberculosis. A few cases of possible primary tuberculous esophagitis have been described. This report describes a patient with dysphagia who appeared to have esophageal tuberculosis without HIV and in the absence of other signs of tuberculosis. The patient responded promptly to treatment with tuberculostatics.

Objective To verify brain eigenfrequency shifting after the occurrence of a lesion producing mass effect into the cranial vault. Design Experimental animal study. Setting Laboratory of experimental surgery affiliated with a university critical care department. Subjects Six adult male New Zealand white rabbits. Interventions A Camino ICP monitor was placed in the parenchyma, and a 5-Fr balloon-tipped catheter and accelerometer were placed into the epidural space. Measurements Before and after the introduction of successive 0.1-mL increments of autologous blood into the balloon, intracranial pressure (ICP) was recorded along with the accelerometer signal obtained during free vibration of the skull triggered by a calibrated hammer. Fast Fourier transformation of the digitized signal provided the eigenfrequency spectrum. The eigenfrequency showing the sharpest decrease after the initial 0.1-mL volume addition was considered as the best frequency, and its variation in response to subsequent 0.1-mL increments represents the brain eigenfrequency shifting. Main Results Brain eigenfrequency shifting to lower values occurs for small blood volume increments (up to 0.2 mL). When volume addition becomes >or=to0.3 mL, brain eigenfrequency shifting to higher values is exhibited. The decrease in best frequency after the initial introduction of 0.1 mL is statistically significant (p = .003), in a range of volume in which no significant intracranial pressure difference appears. The respective variation of ICP is explained using a quadratic curve. For volumes of 0 to 0.1 mL, the change in ICP is not statistically significant (p = .08). Conclusions Changes of the brain's physical characteristics by mass addition in the cranial vault can be expressed by brain eigenfrequency shifting. The method seems advantageous because it reliably detects mass additions at low levels where no ICP change occurs. Additionally, it provides serial measurements, and it is less invasive than the currently used methods for intracranial compliance. (Crit Care Med 1999; 27:978-984)

Infectious mononucleosis, most commonly caused by Epstein-Barr virus (EBV), generally results in mild, self-limited illness characterized by fever, pharyngitis and lymphadenopathy. The young woman presented in our case report had clinical and serologic evidence of infectious mononucleosis and developed cervical abscess, which directly extended into the retropharyngeal space, mediastinum and the pleural spaces without lung involvement. After antibiotic and extensive surgical treatment she made a full recovery.

Background To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation. Methods Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs). Results Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham. Conclusion The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.

Dear Sir: Refering to the Physiological Note of Amal Jurban “Pulse Oximetry” which was published in the issue of Intensive Care Medicine of July 24th 2004, we would like to make two additional statements. One very useful clinical application of pulse oximetry which has not been mentioned in the article above is that the cyclical respiratory induced changes in the amplitude of the pulse oximeter waveform can be used to detect normotensive hypovolemia. According to several studies [1, 2], systolic pressure variation and its dDown component have been shown to be sensitive factors in estimating intravascular volume in patients undergoing mechanical ventilation. Therefore respiratory-induced waveform variability of the pulse oximetric signal is a useful measurement in the detection of mild hypovolemia. Furthermore, as far as limitations of pulse oximetry are concerned, an important question which evokes is what happens with increasing bilirubin concentrations. According to several studies [3] hyperbilirubinemia does not interfere with hemoglobin saturation measured by pulse oximetry, while others [4] suggest that a bilirubin concentration below 17mg/dl is a safe limit above which measurements exceed normal values. The later stands for multiwavelength oximeters because in severe jaundice the O2Hb values are not identical with the real blood concentration of this hemoglobin deritive. In this situation pulse oximetry is more valid.

Introduction Azoles, and specifically itraconazole, are often prescribed for the treatment of fungal diseases or empirically for persistent sepsis in patients who are neutropenic or in intensive care. Occasional cardiovascular adverse events have been associated with itraconazole use, and are usually attributed to the interaction of itraconazole with cisapride, terfenadine or digoxin. Its interaction with amiodarone has not been previously described. Case presentation A 65-year-old Caucasian man was admitted to the Intensive Care Unit at our facility for an extensive ischemic stroke associated with atrial fibrillation. Due to rapid ventricular response he was started on intravenous amiodarone and few days later itraconazole was also prescribed for presumed candidemia. After receiving the first dose our patient became profoundly hypotensive but responded rapidly to fluids and adrenaline. Then, two months later, itraconazole was again prescribed for confirmed fungemia. After receiving the first dose via a central venous catheter our patient became hypotensive and subsequently arrested. He was resuscitated successfully, and as no other cause was identified the arrest was attributed to septic shock and his antifungal treatment was changed to caspofungin. When sensitivity test results became available, antifungal treatment was down-staged to itraconazole and immediately after drug administration our patient suffered another arrest and was once again resuscitated successfully. This time the arrest was related to itraconazole, which was discontinued, and from then on our patient remained stable until his discharge to our neurology ward. Conclusions Itraconazole and amiodarone coadministration can lead to serious cardiovascular adverse events in patients who are critically ill. Intensivists, pharmacists and medical physicians should be aware of the interaction of these two commonly used drugs.