Update in intensive care medicine: Studies that challenged our practice in the last 5 years
ABSTRACTDuring the last 5 years, new randomized trials in critically ill patients have challenged a number of traditional treatment strategies in intensive care. The authors review eight studies that helped change their medical practices.
KEY POINTS
- In patients with acute respiratory distress syndrome (ARDS), fluid restriction is associated with better outcomes. A pulmonary arterial catheter is not indicated in the routine management of ARDS. Corticosteroid use can result in improved oxygenation but may be associated with worse outcomes if treatment is started late, ie, more than 14 days after the onset of the disease.
- Intensive insulin therapy is associated with hypoglycemia and may be associated with complications in medical patients.
- In patients with septic shock, corticosteroid therapy is associated with faster shock reversal, but its effects on mortality rates remain controversial. Vasopressin improves hemodynamic variables but is not associated with a lower mortality rate.
- Daily interruption of sedation and early awakening of mechanically ventilated patients result in better outcomes.
- Compared with norepinephrine, dopamine is associated with more cardiac adverse events in patients with shock.
Interrupting sedation was superior
The combination of sedation interruption and a spontaneous breathing trial was superior to a spontaneous breathing trial alone. The mean number of ventilator-free days:
- 14.7 ± 0.9 with sedation interruption
- 11.6 ± 0.9 days with usual care (P = .02).
The median time to ICU discharge:
- 9.1 days with sedation interruption (interquartile range 5.1 to 17.8)
- 12.9 days with usual care (interquartile range 6.0 to 24.2, P = .01).
The mortality rate at 28 days:
- 28% with sedation interruption
- 35% with usual care (P = .21).
The mortality rate at 1 year:
- 44% with sedation interruption
- 58% with usual care (hazard ratio [HR] in the intervention group 0.68, 95% CI 0.50–0.92, P = .01).
Of note, patients in the intervention group had a higher rate of self-extubation (9.6% vs 3.6%, P = .03), but the rate of reintubation was similar between the groups (14% vs 13%, P = .47).
Comments
The addition of daily awakenings to spontaneous breathing trials results in a further reduction in the number of ICU days and increases the number of ventilator-free days.
Of note, the protocol allowed patients in the control group to undergo a spontaneous breathing trial while on sedatives (69% of the patients were receiving sedation at the time). Therefore, a bias effect in favor of the intervention group cannot be excluded. However, both groups had to meet criteria for readiness for spontaneous breathing.
The study demonstrates the safety of daily awakenings and confirms previous findings suggesting that a daily trial of spontaneous breathing results in better ICU outcomes.
GLUCOSE CONTROL IN THE ICU
Key points
- Although earlier studies suggested that intensive insulin therapy might be beneficial in critically ill patients, new findings show that strict glucose control can lead to complications without improving outcomes.
Background
A previous study15 found that intensive insulin therapy to maintain a blood glucose level between 80 and 110 mg/dL (compared with 180–200 mg/dL) reduced the mortality rate in surgical critical care patients. The mortality rate in the ICU was 4.6% with intensive insulin therapy vs 8.0% with conventional therapy (P < .04), and the effect was more robust for patients who remained longer than 5 days in the ICU (10.6% vs 20.2%).
Importantly, however, hypoglycemia (defined as blood glucose ≤ 40 mg/dL) occurred in 39 patients in the intensive-treatment group vs 6 patients in the conventional-treatment group.
The NICE-SUGAR trial
NICE-SUGAR STUDY INVESTIGATORS; FINFER S, CHITTOCK DR, SU SY, ET AL. INTENSIVE VERSUS CONVENTIONAL GLUCOSE CONTROL IN CRITICALLY ILL PATIENTS. N ENGL J MED 2009; 360:1283–1297.
The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial16 randomized 6,104 patients in medical and surgical ICUs to receive either intensive glucose control (blood glucose 81–108 mg/dL) with insulin therapy or conventional glucose control (blood glucose < 180 mg/dL). In the conventional-control group, insulin was discontinued if the blood glucose level dropped below 144 mg/dL.
A higher mortality rate with intensive glucose control
As expected, the intensive-control group achieved lower blood glucose levels: 115 vs 144 mg/dL.
Nevertheless, intensive glucose control was associated with a higher incidence of severe hypoglycemia, defined as a blood glucose level lower than 40 mg/dL: 6.8% vs 0.5%.
More importantly, compared with conventional insulin therapy, intensive glucose control was associated with a higher 90-day mortality rate: 27.5% vs 24.9% (odds ratio 1.14, 95% CI 1.02–1.28). These findings were similar in the subgroup of surgical patients (24.4% vs 19.8%, odds ratio 1.31, 95% CI 1.07–1.61).
Comments
Of note, the conventional-control group had more patients who discontinued the treatment protocol prematurely. Additionally, more patients in this group received corticosteroids.
These results widely differ from those of a previous study by van den Berghe et al,15 which showed that tight glycemic control is associated with a survival benefit. The differences in outcomes are probably largely related to different patient populations, as van den Berghe et al included patients who had undergone cardiac surgery, who were more likely to benefit from strict blood glucose control.
The VISEP trial
BRUNKHORST FM, ENGEL C, BLOOS F, ET AL; GERMAN COMPETENCE NETWORK SEPSIS (SEPNET). INTENSIVE INSULIN THERAPY AND PENTASTARCH RESUSCITATION IN SEVERE SEPSIS. N ENGL J MED 2008; 358:125–139.
The Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) trial was a multicenter study designed to compare intensive insulin therapy (target blood glucose level 80–110 mg/dL) and conventional glucose control (target blood glucose level 180–200 mg/dL) in patients with severe sepsis.17 It also compared two fluids for volume resuscitation: 10% pentastarch vs modified Ringer's lactate. It included both medical and surgical patients.
Trial halted early for safety reasons
The mean morning blood glucose level was significantly lower in the intensive insulin group (112 vs 151 mg/dL).
Severe hypoglycemia (blood glucose ≤ 40 mg/dL) was more common in the group that received intensive insulin therapy (17% vs 4.1%, P < .001).
Mortality rates at 28 days did not differ significantly: 24.7% with intensive control vs 26.0% with conventional glucose control. The mortality rate at 90 days was 39.7% in the intensive therapy group and 35.4% in the conventional therapy group, but the difference was not statistically significant.
The intensive insulin arm of the trial was stopped after 488 patients were enrolled because of a higher rate of hypoglycemia (12.1% vs 2.1%) and of serious adverse events (10.9% vs 5.2%).
Additionally, the fluid resuscitation arm of the study was suspended at the first planned interim analysis because of a higher risk of organ failure in the 10% pentastarch group.
