Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock (30 vs. 46.5 percent mortality). This has subsequently been tested in 3 multicenter randomized control trials (PROCESS, PROMISE, ARISE) which have not shown protocolized sepsis care following EGDT to be better than standard care.
Bellomo. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000;356:2139-43
In a multicentre, randomised, controlled, double-blind study comparing low-dose dopamine (2μg/kg/min) infusion with placebo in 328 patients with at least two SIRS criteria and early renal dysfunction, there were no differences in peak serum creatinine concentration (dopamine 245 vs placebo 249 μmol/L; p=0·93), increase in serum creatinine from baseline to highest value (62 vs 66 μmol/L; p=0·82), patients whose serum creatinine concentration exceeded 300 μmol/L (56 vs 56; p=0·92), requirement for renal replacement therapy (35 vs 40; p=0·55), duration of ICU stay (13 vs 14 days; p=0·67), duration of hospital stay (29 vs 33 days; p=0·29), or mortality (69 deaths versus 66 deaths).
In a multicentre, double-blind, randomized placebo-controlled trial comparing hydrocortisone (50mg IV 6 hourly, then tapered) with placebo in 499 patients with septic shock, there was no significant difference in 28-day mortality (hydrocortisone group 34.3% vs placebo group 31.5%; P=0.51). Subgroup analyses of 28-day mortality based on response to corticotropin also showed no difference between study groups. Hydrocortisone hastened reversal of shock compared to placebo, however, with more episodes of superinfection, including new sepsis and septic shock.
No significant advantage, with respect to mortality or morbidity, of protocol-based resuscitation over bedside care that was provided according to the treating physician's judgement.
In a blinded, multicenter, randomized control trial, comparing noradrenaline plus dobutamine with adrenaline in 330 patients with septic shock, aiming to maintain mean arterial pressure at 70 mmHg, there were no significant differences in 28 day mortality (34% vs. 40%, relative risk 0.86, 95% CI 0.65 to 1.14, P=0.31), ICU mortality (47%s vs 75, p=0·69), hospital mortality (52% vs 49%, p=0·51), 90 day mortality (52% vs 50%, p=0·73), time to haemodynamic success (p=0·67), time to vasopressor withdrawal (p=0·09), or rates of serious adverse events.
In a blinded, multicenter, randomized, control trial, comparing activated protein C (24 µg/kg/hr for 96 hours) with a placebo, in 1,697 adults with septic shock, there were no significant differences in mortality at 28 (26.4% vs. 24.2%, relative risk with APC 1.09, 95% CI 0.92 to 1.28 P=0.31) or 90 days (34.1% versus 32.7%, relative risk with APC 1.04, 95% CI 0.90 to 1.19, P=0.56), including those with initially low levels of APC (28 day mortality 28.7% vs. 30.8%, RR 0.93, 95% CI 0.74 to 1.17; p=0.54), or difference in serious bleeding (APC 10 patients versus placebo 8 patients, P=0.81).
In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days.
Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality.
Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors.
The use of hydrocortisone did not decrease mortality in a general population of patients with septic shock, even though the drug hastened reversal of shock
DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.
Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events.
Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients.
No efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days.
2015 - Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection (NEJM)
Pts 16 yrs or older w/ intraabdominal infection AND fever, leukocytosis, OR ileus precluding intake of more than half their normal diet AND undergone source control intervention
Mean age 52
Most common infection site = colon or rectum > appendix > small bowel
Most common souce control procedure = percutaneous drainage
RCT, 23 sites: 4 full days of abx after source control (257 pts, experimental) vs. abx continued until 2 days after resolution of SIRS, max 10 day duration (260 pts, control)
No significant differences in baseline characteristics
Similar composite surgical-site infection, recurrent intraabdominal infection, or death rate (21.8% experimental vs. 22.3% control)
No difference even when rates were compared individually
No difference even when looking at just the proportion of pts that adhered to protocol (81.8% of experimental, 72.7% of control)
Longer days to diagnosis of surgical site infection in control group by ~6 days
Longer days to diagnosis of recurrent intraabdominal infection in control group by ~4 days
Similar days to death
All deaths were not related to initial intraabdominal infection but to coexisting diseases
Duration of abx 4.0 days in experimental vs. 8.0 days in control
No difference in rates of extraabdominal infection, C. diff, or secondary infection with resistant pathogens
No difference in hospitalization length of stay
In pts with intraabdominal infections who had undergone adequate source control procedure, outcomes after 4 days of abx were similar to those after a longer course of abx that extended until resolution of physiological abnormalities
Of note, original sample size calculated to power this study was 505 pts PER GROUP, but this study was stopped early due to interim analysis showing no difference in outcomes