26 Jan 08
Posted in Anesthesia at 18:39 by Laci
By P Myles, K Leslie, M Chan, A Forbes, MJ Paech, P Peyton, B Silbert, EB Pascoe, the ENIGMA Trial Group
Anesthesiology 2007;107:221-231
Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear.
Methods
Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery.
Results
Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02).
Conclusions
Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.
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Posted in Anesthesia at 18:35 by Laci
By H Hopf
Anesthesiology 2007;102:200-201
During the past decade, anesthesiologists have increasingly recognized that the effects of anesthesia reach beyond the postanesthesia care unit. Researchers have extended their vision beyond studies of pain and postoperative nausea and vomiting in the postanesthesia care unit (still important outcomes) to studies of the impact of anesthesia on a broad range of postoperative outcomes, including cardiac complications and surgical wound infection. Myles et al.,1 in this issue of Anesthesiology, report an outstanding, large (2,050 patients), multicenter, pragmatic randomized controlled trial of the effect of intraoperative gas selection on a wide range of postoperative complications. Patients undergoing major surgery were randomly assigned to receive 80% oxygen with 20% nitrogen versus 30% oxygen with 70% nitrous oxide intraoperatively. Patients assigned to the high inspired oxygen-nitrous oxide avoidance group had fewer major postoperative complications and less frequent severe postoperative nausea and vomiting, and were more rapidly discharged from the intensive care unit, although hospital stay did not differ between groups. The authors conclude, The routine use of nitrous oxide in patients undergoing major surgery should be questioned. An alternative conclusion would be that the routine use of high inspired oxygen (which precludes high inspired nitrous oxide) in patients undergoing major surgery should become routine.
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13 Jan 08
Posted in Glucose control, Sepsis at 17:58 by Laci
By F M Brunkhorst, C Engel, F Bloos, A Meier-Hellmann, M Ragaller, N Weiler, O Moerer, M Gruendling, et al for the German Competence Network Sepsis (SepNet)
NEJM 2008:358;125-139
The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.
Methods
In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer’s lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.
Results
The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.
Conclusions
The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses.
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Posted in Sepsis, Steroid at 17:55 by Laci
By C L Sprung, D Annane, D Keh, R Moreno, M Singer, K Freivogel, Y G Weiss et al for the CORTICUS Study Group
NEJM 2008;358:111-124
Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.
Methods
In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.
Results
Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.
Conclusions
Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed.
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