What change in outcomes after cardiac arrest is necessary to change practice? Results of an international survey.

BACKGROUND: Efficient trials of interventions for patients with out-of-hospital cardiac arrest (OHCA) should have adequate but not excess power to detect a difference in outcomes. The minimum clinically important difference (MCID) is the threshold value in outcomes observed in a trial at which providers should choose to adopt a treatment. There has been limited assessment of MCID for outcomes after OHCA. Therefore, we conducted an international survey of individuals interested in cardiac resuscitation to define the MCID for a range of outcomes after OHCA. METHODS: A brief survey instrument was developed and modified by consensus. Included were open-ended responses. The survey included an illustrative example of a hypothetical randomized study with distributions of outcomes based on those in a public use datafile from a previous trial. Elicited information included the minimum significant difference required in an outcome to change clinical practice. The population of interest was emergency physicians or other practitioners of acute cardiovascular research. RESULTS: Usable responses were obtained from 160 respondents (50% of surveyed) in 46 countries (79% of surveyed). MCIDs tended to increase as baseline outcomes increased. For a population of patients with 25% survival to discharge and 20% favorable neurologic status at discharge, the MCID were median 5 (interquartile range [IQR] 3, 10) percent for survival to discharge; median 5 (IQR 2, 10) percent for favorable neurologic status at discharge, median 4 (IQR 2, 9) days of ICU-free survival and median 4 (IQR 2, 8) days of hospital-free survival. CONCLUSION: Reported MCIDs for outcomes after OHCA vary according to the outcome considered as well as the baseline rate of achieving it. MCIDs of ICU-free survival or hospital-free survival may be useful to accelerate the rate of evidence-based change in resuscitation care.

Randomized pilot trial of intensive management of blood pressure or volume expansion in subarachnoid hemorrhage (IMPROVES).

BACKGROUND: Volume expansion and hypertension are widely used for the hemodynamic management of patients with subarachnoid hemorrhage. OBJECTIVE: To investigate the feasibility, adherence, and retention in a trial of volume expansion and blood pressure manipulation to prevent delayed cerebral ischemia. METHODS: A randomized pilot trial using a 2-way factorial design allocating patients within 72 hours of subarachnoid hemorrhage to either normovolemia (NV) or volume expansion (HV) and simultaneously to conventional (CBP) or augmented blood pressure (ABP) for 10 days. The study endpoints were protocol adherence and retention to follow-up. The quality of endpoints for a larger trial were 6-month modified Rankin Scale score, comprehensive neurobehavioral assessment, delayed cerebral ischemia, new stroke, and discharge disposition. RESULTS: Twenty patients were randomized and completed follow-up. The overall difference in daily mean intravenous fluid intake was 2099 mL (95% confidence interval [CI]: 867, 3333), HV vs NV group. The overall mean systolic blood pressure difference was 5 mm Hg (95% CI: -4.65, 14.75), ABP vs CBP group. Adverse events included death (n=1), delayed cerebral ischemia (n=1), and pulmonary complications (n=3). There were no differences in modified Rankin Scale score between HV and NV (difference 0.1; 95% CI: -1.26, 1.46, P=.87) or between ABP and CBP groups (-0.5, 95% CI: -1.78, 0.78, P=.43). Neuropsychological scores were similar between HV vs NV, but tended to be worse in ABP (57±27) vs CBP group (85±21, P=.04). CONCLUSION: This pilot study showed adequate feasibility and excellent retention to follow-up. Given the suggestion of possible worse neurobehavioral outcome with ABP, a larger trial to determine the optimal blood pressure management in this patient population is warranted. (ClinTrials.gov NCT01414894.)

A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation.

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were $1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.

Risk tolerance and bile duct injury: surgeon characteristics, risk-taking preference, and common bile duct injuries.

BACKGROUND: Little is known about surgeon characteristics associated with common bile duct injury (CBDI) during laparoscopic cholecystectomy (LC). Risk-taking preferences can influence physician behavior and practice. We evaluated self-reported differences in characteristics and risk-taking preference among surgeons with and without a reported history of CBDI. STUDY DESIGN: A mailed survey was sent to 4,100 general surgeons randomly selected from the mailing list of the American College of Surgeons. Surveys with a valid exclusion (retired, no LC experience) were considered responsive, but were excluded from data analysis. RESULTS: Forty-four percent responded (1,412 surveys analyzed), 37.7% reported being the primary surgeon when a CBDI occurred, and 12.9% had more than one injury. Surgeons reporting an injury were slightly older (52.8 +/- 9.0 years versus 51.3 +/- 9.8 years; p < 0.004) and in practice longer (20.8 +/- 9.7 years versus 18.9 +/- 10.5 years; p < 0.001). Surgeons not reporting a CBDI were more likely trained in LC during residency (63.3% versus 55.4% injuring) as compared with surgeons reporting a CBDI, who were more likely trained at an LC course (29.8% versus 38.2%). Surgeons in academic practice or who work with residents had lower reported rates of CBDI (7.9% versus 14.5% [academics]; 18.7% versus 25.0% [residents]). Mean risk score was 12.4 +/- 4.4 (range 6 to 30 [30 = highest]) with a similar average between those who did (12.2 +/- 4.5) and did not (11.9 +/- 4.4) report a CBDI (p < 0.23). Compared with surgeons in the lowest three deciles of risk score, relative risk for CBDI among surgeons in the upper three deciles was 17% greater (p = 0.07). CONCLUSIONS: More years performing LC and certain practice characteristics were associated with an increased rate of CBDI. The impact of extremes of risk-taking preference on surgical decision making can be an important part of decreasing adverse events during LC and should be evaluated.