A retrospective study covering a 14-year period was carried out to estimate the incidence and assess the clinical features of benzodiazepine (BZD) poisoning. The annual contribution of BZDs to the total number of drug overdose cases admitted to an intensive care unit displayed an increasing trend over the period, and during the last years BZDs were involved in nearly one-third of all cases. Among the 702 cases of BZD overdosage, 144 had ingested BZD alone, 200 had poisoned themselves with BZD combined with alcohol and 358 had taken BZD with other miscellaneous drugs. In 56% of all the cases the patients had severe central nervous system depression on admission. In 47% orotracheal intubation was performed and in 18% artificial ventilation was administered. Complications were recorded in 69 of the 702 cases (9.8%) and five cases were fatal. These clinical features were essentially the same in the group that had overdosed with just BZD. In conclusion, patients with drug overdosage involving BZD have a low hospital mortality, but the acute somatic risk is not negligible. Moreover, they consume a substantial proportion of the resources in the emergency room and the intensive care unit.

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Patients without respiratory symptoms were studied awake and during general anesthesia with mechanical ventilation prior to elective surgery. Ventilation-perfusion (VA/Q) relationships, gas exchange and atelectasis formation were studied during five different conditions: 1) supine, awake; 2) supine during anesthesia with conventional mechanical ventilation (CV); 3) in the left lateral position during CV; 4) as 3) but with 10 cm of positive end-expiratory pressure (PEEP) and 5) as 3) but using differential ventilation with selective PEEP (DV + SPEEP) to the dependent lung. Atelectatic areas and increases of shunt blood flow and blood flow to regions with low VA/Q ratios appeared after induction of anesthesia and CV. With the patients in the lateral position, further VA/Q mismatch with a fall in PaO2 and increased dead space ventilation was observed. Atelectatic lung areas were still present, although the total atelectatic area was slightly decreased. Some of the effects caused by the lateral position could be counteracted by adding PEEP. Perfusion of regions with low VA/Q ratios and venous admixture were then diminished, while PaO2 was slightly increased; shunt blood flow and dead space ventilation were essentially unchanged. During CV + PEEP, there was a decrease in cardiac output, compared to CV in the lateral position. DV + SPEEP was more effective than CV + PEEP in decreasing shunt flow and increasing PaO2 in the lateral position; in addition to this, cardiac output was not affected.

Objective-To assess the diagnostic value and safety of the benzodiazepine antagonist flumazenil in patients with coma ofunclear origin with suspected poisoning.Design-Double blind, placebo controlled, randomised study.Setting-Intensive care unit at a major teaching hospital.Patients-105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score >10 on a scale graded from 4 to 20. Patients were allocated randomly to receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women).Interventions -Intravenous injection offlumazenil (10 ml, 0-1 mg/ml) or placebo (10 ml vehicle alone) given double blind over three minutes.Main outcome measures -Serum and urine concentrations ofbenzodiazepines, antidepressants, and several other agents; blood gas tensions; standardised evaluation on admission and five minutes after the injection by means of coma scale score and urgent diagnostic or therapeutic interventions indicated according to the history and clinical examination; standardised interview after the injection to try to ascertain further information; and adverse reactions.Results-Benzodiazepines were found in the serum in 36 of the 53 patients in the flumazenil group and in 37 of the 52 who received placebo. The average coma scale score increased significantly after injection in the flumazenil group (6-4 v 12-1, p<0-001) but not in the placebo group. In the flumazenil group several interventions were rendered unnecessary by the injection: gastric lavage and urinary catheterisation (19 patients each), intubation (21), artificial ventilation and computed tomography of the brain (three patients each), blood culture and lumbar puncture (one patient each), and electroencephalography (two). In the placebo group the indications for these procedures did not change in any patient after injection. The 95% confidence interval for the difference in reduction of the frequency ofindications for gastric lavage after injection between the two groups was 21% to 51%, that for intubation 25% to 55%, and that for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave valuable information on their drug ingestion within 10 minutes after injection compared with only one in the placebo group (p<0-001). Nine adverse reactions were recorded in the flumazenil group, eight of which were graded as mild and one severe.