Pinhas Halpern

Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison

Objective: To compare the efficacy, safety, and cost of midazolam and propofol in prolonged sedation of critically ill patients.Design: Randomized, prospective study.Setting: General intensive care unit (ICU) in a 1100-bed teaching hospital.Patients: 67 critically ill, mechanically ventilated patients.Interventions: Patients were invasively monitored and mechanically ventilated. A loading dose [midazolam 0.11 ± 0.02 (SEM) mg · kg−1, propofol 1.3 ± 0.2 mg · kg−1] was administered, followed by continuous infusion, titrated to achieve a predetermined sedation score. Sedation was continued as long as clinically indicated.Measurements and results: Mean duration of sedation was 141 and 99 h (NS) for midazolam and propofol, respectively, at mean hourly doses of 0.070 ± 0.003 mg · kg−1 midazolam and 1.80 ± 0.08 mg · kg−1 propofol. Overall, 68 % of propofol patients versus 31 % of midazolam (p<0.001) patients had a > 20 % decrease in systolic blood pressure after the loading dose, and 26 versus 45 % (p<0.01) showed a 25 % decrease in spontaneous minute volume. Propofol required more daily dose adjustments (2.1 ± 0.1 vs 1.4 ± 0.1, p<0.001). Nurserated quality of sedation with midazolam was higher (8.2 ± 0.1 vs 7.3 ± 0.1 on a 10-cm visual analog scale, p<0.001). Resumption of spontaneous respiration was equally rapid. Recovery was faster after propofol (p<0.02), albeit with a higher degree of agitation. Amnesia was evident in all midazolam patients but in only a third of propofol patients. The cost of propofol was 4–5 times higher.Conclusions: Both drugs afforded reliable, safe, and controllable long-term sedation in ICU patients and rapid weaning from mechanical ventilation. Midazolam depressed respiration, allowed better maintenance of sedation, and yielded complete amnesia at a lower cost, while propofol caused more cardiovascular depression during induction.

Soluble tumor necrosis factor receptors reduce bowel ischemia-induced lung permeability and neutrophil sequestration

OBJECTIVES To evaluate the possible role of tumor necrosis factor (TNF) in the development of lung injury after bowel ischemia, and the ability of TNF-soluble receptors to negate TNF toxicity, using a rat small bowel ischemia and reperfusion model. DESIGN Prospective, randomized, controlled laboratory study. SETTING Research laboratory. SUBJECTS Forty adult male Sprague-Dawley rats weighing approximately 300 g. INTERVENTIONS The rats were divided equally into four groups: a) ischemia and reperfusion alone; b) those animals receiving TNF antibodies (1 mL) before reperfusion; and c) those animals receiving 200 micrograms of human recombinant TNF soluble receptors. These 30 anesthetized rats underwent 60 mins of superior mesenteric artery occlusion per 4 hrs of reperfusion. The remaining ten animals were sham operated (laparotomy), serving as controls. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. MEASUREMENTS AND MAIN RESULTS Thirty and 60 mins after declamping and reperfusion, plasma TNF concentrations increased to 830 +/- 66 and 173 +/- 56 pg/mL, respectively, compared with 10 pg/mL before ischemia (p < .001). In sham-operated control rats, TNF concentrations did not increase from baseline concentrations. Four hours after reperfusion, sequestration of neutrophils in the pulmonary microcirculation was noted (319 +/- 60 vs. 84 +/- 13 neutrophils/10 high-power fields in sham-operated rats [p < .04]). Pulmonary microvascular leak also occurred, as measured by translocation of radiolabeled albumin into the bronchoalveolar space and expressed as the ratio of bronchoalveolar lavage to blood concentrations. This ratio was 5.3 +/- 0.8 in ischemic control animals compared with 1.1 +/- 0.3 in sham animals (p < .03). Treatment with antibodies to TNF before reperfusion attenuated the pulmonary injury (75 +/- 6 neutrophils/10 high-power fields, permeability index 1.6 +/- 0.1) less than in ischemic controls (p < .005). A similar protection was achieved with soluble TNF receptors, which prevented bowel ischemia-induced lung neutrophil sequestration (117 +/- 35 neutrophils/10 high-power fields, pulmonary vascular leak ratio of 2.3 +/- 0.1, p < .05). CONCLUSIONS The results of this study show that ischemia and subsequent reperfusion of the intestine in rats produce lung injury. This injury is mediated, at least in part, by TNF. Soluble TNF receptors are an effective tool in preventing lung TNF injury after intestinal ischemia.

The use of flumazenil in the management of acute drug poisoning — a review

The popularity and widespread availability of benzodiazepines (BZD) has led to their frequent abuse in intentional drug poisoning. Although mortality from pure BZD overdose is usually small, in elderly, debilitated patients, or when BZD are combined with other CNS depressant drugs, morbidity increases significantly and outcome may be fatal. Drug overdose is therefore a medical emergency necessitating close obervation and support of vital functions. Recently, the specific BZD antagonist flumazenil (Anexate®) has become clinically available and much experience in its usefulness has accumulated. The present review summarizes a total of 30 studies and reports published to date, involving approximately 760 intoxicated patients. Flumazenil was evaluated both in prehospital use as well as in emergency rooms or in intensive care units. The age of patients ranged from 4–90 years and doses of flumazenil varied between 0.3–10 mg, approximately 1 mg being the most frequently used. All patients intoxicated with only BZD returned to full consciousness within minutes after the injection of flumazenil. When a mixture of BZD and other CNS depressants was abused, a range of effects was observed. This varied from no change to a return to full orientation, depending on the contribution of the BZD to the state of unconsciousness. Re-sedation occurred in about 65% of flumazenil treated patients, usually within 0.5–3 h after the first dose, the shorter interval being associated with mixed-drug poisoning. Repeated doses of the antagonist (0.2–2 mg), sometimes followed by continuous infusion (0.1–0.5 mg/h), were effective in maintaining patients fully oriented. Of 78 intubated patients 27% could be extubated safely while in 14 instances intubation was avoided following arousal with flumazenil. General and local tolerance to flumazenil were excellent. No significant hemodynamic changes were observed. Side effects (anxiety, agitation, etc.) occured in one third of the patients and were mild and self-limited. Seven (out of the 760) patients developed convulsions, attributable to either rapid injection of a high dose of the drug or to combination of BZD and cyclic antidepressants. The efficacy and safety of flumazenil in reversing coma due to BZD intoxication has been confirmed in this large number of studies. It is recommended that flumazenil be given by slow titration and that patients remain under close observation to guard against re-sedation.

C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department

IntroductionC-reactive protein (CRP) is a real-time and low-cost biomarker to distinguish febrile bacterial infections from non-bacterial febrile illnesses. We hypothesised that measuring the velocity of the biomarker instead of its absolute serum concentration could enhance its ability to differentiate between these two conditions.MethodsWe prospectively recruited adult patients (age ≥ 18 years) who presented to the emergency department with fever. We recorded their data regarding the onset of fever and accompanying symptoms. CRP measurements were obtained upon admission. CRP velocity (CRPv) was defined as the ratio between CRP on admission and the number of hours since the onset of fever. Patients were diagnosed by clinical symptoms, blood cultures and imaging studies, and the diagnoses were confirmed by an infectious disease specialist. The efficacy of CRPv as a diagnostic marker was evaluated by using receiver operator curves (ROC). Excluded were patients who did not know the time fever started with certainty, patients with malignancy, patients with HIV infection and patients who had been using antibiotics upon presentation.ResultsOf 178 eligible patients, 108 (60.7%) had febrile bacterial infections (mean CRP: 63.77 mg/L, mean CRPv: 3.61 mg/L/hour) and 70 (39.3%) had non-bacterial febrile illnesses (mean CRP: 23.2 mg/L, mean CRPv: 0.41 mg/L/hour). The area under the curve for CRP and CRPv were 0.783 (95% confidence interval (CI) = 0.717 to 0.850) and 0.871 (95% CI = 0.817 to 0.924), respectively. In a 122-patient subgroup with a CRP level of less than 100 mg/L, the area under the curve increased from 0.689 (95% CI = 0.0595 to 0.782) to 0.842 (95% CI = 0.77 to 0.914) by using the CRPv measurements.ConclusionsCRPv improved differentiation between febrile bacterial infections and non-bacterial febrile illnesses compared with CRP alone, and could identify individuals who need prompt therapeutic intervention.

Ultrasonography for the evaluation of abdominal trauma in multiple casualty incidents

Objective: Ultrasound (US) is commonly used for the diagnosis of hemoperitoneum in trauma patients. The use of US in the evaluation of abdominal injury during multiple casualty incidents (MCIs) has been described, but never evaluated. The purpose of this study was to determine the accuracy of US for evaluation of the unique injury patterns associated with MICs. Patients and methods: We conducted a retrospective study of patients admitted to a Level 1 trauma center during MCIs resulting from terrorist attacks in the Tel‐Aviv area. Results: During the 4‐year study period there were 43 patients who had an US examination as part of their initial assessment. The overall accuracy of the US examination was 77%, with a sensitivity of 40%, and a specificity of 88%. The positive predictive value (PPV) was 50%, and the negative predictive value (NPV) was 83%. Conclusions: Although US examination lacks the sensitivity to be used alone in determining operative intervention in the evaluation of patients admitted in an ...