Journal watch: Recent studies of note
From the April ACP Hospitalist, copyright © 2008 by the American College of Physicians
“Open-lung” ventilation in acute lung injury and ARDS
Patients with acute lung injury and the acute respiratory distress syndrome (ARDS) may benefit from a ventilation strategy based on the “open-lung approach,” a recent study reported.
The established treatment method for patients with acute lung injury and ARDS involves ventilation with low tidal volumes, which has been shown to improve survival. However, it has been suggested that adding measures to open collapsed lung tissue would lead to increased benefit. Canadian researchers performed a randomized, controlled trial at 30 hospitals to determine whether a “lung open ventilation” (LOV) strategy that combined lung recruitment maneuvers, high levels of positive end-expiratory pressure and low tidal volumes would improve mortality rates in patients with acute lung injury. The study appears in the Feb. 13 Journal of the American Medical Association.
Researchers randomly assigned patients to receive LOV (476 patients) or control ventilation (509 patients). The main outcome measure was all-cause hospital mortality. Of the 983 study patients included in the primary analysis, 85% were considered to have ARDS at enrollment. Rates of all-cause hospital mortality were 36.4% in the LOV group and 40.4% in the control group (relative risk, 0.90 [95% CI, 0.77 to 1.05]; P= 0.19), while barotrauma rates were 11.2% and 9.1%, respectively (relative risk, 1.21 [95% CI, 0.83 to 1.75]; P= 0.33]). Rates of refractory hypoxemia, death with refractory hypoxemia and use of rescue therapies were all lower in the LOV group (4.6% vs. 10.2%, 4.2% vs. 8.9% and 5.1% vs. 9.3%, respectively).
The authors concluded that the two strategies resulted in similar mortality rates, but that the LOV strategy led to less frequent use of rescue therapies and fewer deaths related to refractory hypoxemia. The trial was limited by an inability to determine the specific effects of each component of the LOV intervention and by small differences between the study groups in age and presence of sepsis at baseline (the control group was 2.4 years older on average than the LOV group and had a rate of sepsis that was 3.7% higher). However, the authors wrote that their results, in conjunction with those from two earlier major trials, justify the use of higher positive end-expiratory pressure in patients with acute lung injury and ARDS.
Probiotics could be harmful in predicted severe acute pancreatitis
Prophylactic probiotics could have adverse effects in patients with predicted severe acute pancreatitis, according to a study.
Because infectious complications are fairly common in patients with acute pancreatitis and do not usually respond to antibiotics, probiotics have begun to be used along with enteral nutrition as a possible prophylactic measure. However, existing trials showing a benefit with this strategy have been small and of lower methodologic quality. Dutch researchers therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial to better determine the usefulness of probiotics in patients predicted to have severe acute pancreatitis. The results were published in the Feb. 14 online edition of Lancet.
Researchers randomly assigned 153 patients with predicted severe acute pancreatitis to receive a multispecies probiotic preparation, while 145 patients were randomly assigned to placebo. Randomization was done within 72 hours of symptom onset. The primary end point was infectious complications during admission and 90-day follow-up, including infected pancreatic necrosis, bacteremia, pneumonia, urosepsis or infected ascites. Because one patient in each group was incorrectly diagnosed with acute pancreatitis, 152 patients receiving probiotics and 144 receiving placebo were analyzed.
Patient characteristics and disease severity were similar in both groups at baseline. Probiotics did not appear to affect rates of infectious complications (30% in the probiotics group and 28% in the placebo group), but mortality rates were higher in those who received probiotics (16% vs. 6%; relative risk, 2.53 [95% CI, 1.22 to 5.25]). In addition, nine cases of bowel ischemia were seen in the probiotics group compared with zero in the placebo group, and eight of the nine patients with bowel ischemia died.
Probiotic preparations “can no longer be considered to be harmless adjuncts to enteral nutrition, especially in critically ill patients or patients at risk for non-occlusive mesenteric ischaemia,” the authors wrote. Their findings may have differed from those of earlier trials because the study sample was larger and included more critically ill patients, they said. Until more is known about the mechanism of action, the authors recommended against routinely administering probiotics, particularly the formulation used in their study, to patients with predicted severe acute pancreatitis.
Survival of in-hospital cardiac arrest less likely during off hours
Hospitalized patients who have cardiac arrests are more likely to survive if the arrest happens on a weekday, instead of at night or on the weekend, a recent study found.
Researchers compared 58,593 in-hospital cardiac arrests that occurred between 7 a.m. and 11 p.m. with 28,155 arrests that took place during night hours. The data came from 507 hospitals that participated in the National Registry of Cardiopulmonary Resuscitation between 2000 and 2007. The investigators also broke down the arrests between weekdays and weekends and then compared data on survival of the event, 24-hour survival, and survival to discharge, as well as favorable neurological outcomes.
The study found substantially lower rates of survival to discharge (14.7% vs. 19.8%), return of spontaneous circulation for longer than 20 minutes (44.7% vs. 51.1%), survival at 24 hours (28.9% vs. 35.4%), and favorable neurological outcomes (11.0% vs. 15.2%) for patients who arrested during the night. Among cardiac arrests that occurred during the day, survival rates were higher on weekdays than on weekends. The survival rates for cardiac arrests at night were similar throughout the week and about equal to those that occurred during the day on weekends.
The study authors noted that differences in day and night survival were not as large among monitored patients as among unmonitored patients, suggesting the monitoring or some other factor, such as intensive care staff, could improve outcomes. The research also found two areas of the hospital—the emergency department and trauma services—where survival rates did not differ by time of day. The authors noted that those services often have similar staffing at all times, unlike other areas of the hospital.
Based on the data, the study authors concluded that hospitals should focus on hospital-wide processes of care for resuscitation on nights and weekends and that such a focus could potentially improve patient safety and survival following cardiac arrest. The study was published in the Feb. 20 Journal of the American Medical Association.
Treatments for acute renal failure may have similar outcomes
Intermittent hemodialysis and continuous renal replacement therapy (CRRT) yield similar clinical outcomes in patients with acute renal failure, according to a recent study.
Canadian researchers analyzed existing research to determine the best way to manage dialysis in patients with acute renal failure. Of 173 articles that examined dialytic support in patients with acute renal failure and that reported mortality, length of hospital stay, hypotension and need for long-term dialysis, 30 randomized, controlled trials and 8 prospective cohort studies were eligible for review. The results appeared in the Feb. 20 Journal of the American Medical Association.
The authors could draw no conclusions from the data regarding the best indications for or timing of renal replacement therapy. In addition, they found no significant clinical differences between CRRT and intermittent hemodialysis in all-cause mortality or need for long-term dialysis treatment (relative risk, 1.10 [95% CI, 0.99 to 1.23] and 0.91 [95% CI, 0.56 to 1.49], respectively). Patients receiving continuous venovenous hemofiltration had a lower risk for death at doses of 35 mL/kg per hour compared with 20 mL/kg per hour (relative risk, 0.74 [95% CI, 0.63 to 0.88]), while those receiving intermittent hemodialysis had a higher risk for death when cellulosic rather than biocompatible membranes were used (relative risk, 1.23 [95% CI, 1.01 to 1.50]).
Based on their research, the authors presented several suggestions for management of acute renal failure, including:
- Before deciding to start renal replacement therapy, physicians should assess intravascular volume, electrolyte and acid–base status, uremia, nutritional requirements and clinical course, among other variables, and should balance the potential benefit of earlier initiation of therapy against risk.
- Since this study found no clinical difference between CRRT and intermittent hemodialysis, the latter, less expensive method may be preferred for most patients.
- Clinicians may prefer CRRT in critically ill patients with severe hemodynamic instability. The target dose of CRRT, if used, should be 35 mL/kg per hour.
- Clinicians should not use unsubstituted cellulose membranes in patients with acute renal failure.
The authors stressed that these recommendations are based primarily on studies in critically ill patients and noted that few good-quality data are available to guide best practice, probably because of a lack of consensus about the condition and indications for dialytic treatment, limited epidemiologic understanding and poor design and inadequate power of existing studies. Future studies, they wrote, should focus on defining subsets of patients with acute renal failure and on ways to improve outcomes after hospital discharge, and should have adequate power to evaluate clinically meaningful outcomes.
Vasopressin doesn’t improve mortality rates in septic shock
Treatment with vasopressin has no effect on mortality rates compared with norepinephrine in patients with septic shock, according to a study.
Catecholamines are often used for resuscitation in patients with septic shock but have significant adverse effects and may increase mortality rates by affecting cardiac output, blood flow to organs and oxygen delivery. Vasopressin has been used as an adjunct therapy to decrease the need for catecholamines; however, it may also affect blood flow, and its use is based on only two small studies. Australian researchers performed a multicenter randomized, double-blind trial to examine whether vasopressin would improve 28-day mortality rates compared with norepinephrine in patients with septic shock. The results appeared in the Feb. 28 New England Journal of Medicine.
The authors studied 778 patients with sepsis at 27 medical centers who were randomly assigned to receive vasopressin (396 patients) or norepinephrine (382 patients) along with open-label vasopressors. At 28 and 90 days, mortality rates were 35.4% and 43.9% in the vasopressin group and 39.3% and 49.6% in the norepinephrine group. Overall rates of serious adverse events were also similar between groups (10.3% vs. 10.5%, respectively). Among patients with less severe septic shock, those in the vasopressin group had lower 28-day mortality rates (26.5% vs. 35.7%; P= 0.05), but this difference was not seen in patients whose septic shock was more severe (44.0% vs. 42.5%; P= 0.76).
The authors concluded that vasopressin did not improve mortality rates or rates of adverse events compared with norepinephrine in patients with septic shock. Although their results indicated a possible benefit of vasopressin in patients with less severe sepsis, the authors wrote, this finding should be considered hypothesis-generating and should be tested in future studies.
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