Michael A. Gillies

Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review

IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm. OBJECTIVE To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm. DESIGN, SETTING, AND PARTICIPANTS OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014. INTERVENTIONS Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay. RESULTS Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, -0.3% to 13.9%]; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]). CONCLUSIONS AND RELEVANCE In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN04386758.

Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis

BACKGROUND Trials suggest that the use of i.v. hydroxyethyl starch (HES) solutions is associ-ated with increased risk of death and acute kidney injury (AKI) in critically ill patients. It is uncertain whether similar adverse effects occur in surgical patients. METHODS Systematic review and meta-analysis of trials in which patients were randomly allocated to 6% HES solutions or alternative i.v. fluids in patients undergoing surgery. Ovid Medline, Embase, Cinhal, and Cochrane Database of Systematic Reviews were searched for trials comparing 6% HES with clinically relevant non-starch comparator. The primary end-point was hospital mortality. Secondary endpoints were requirement for renal replacement therapy (RRT) and author-defined AKI. Pre-defined subgroups were cardiac and non-cardiac surgery. RESULTS Four hundred and fifty-six papers were identified; of which 19 met the inclusion criteria. In total, 1567 patients were included in the analysis. Dichotomous outcomes were expressed as a difference of proportions [risk difference (RD)]. There was no difference in hospital mortality [RD 0.00, 95% confidence interval (CI) -0.02, 0.02], requirement for RRT (RD -0.01, 95% CI -0.04, 0.02), or AKI (RD 0.02, 95% CI -0.02 to 0.06) between compared arms overall or in predefined subgroups. CONCLUSIONS We did not identify any differences in the incidence of death or AKI in surgical patients receiving 6% HES. Included studies were small with low event rates and low risk of heterogeneity. Narrow CIs suggest that these findings are valid. Given the absence of demonstrable benefit, we are unable to recommend the use of 6% HES solution in surgical patients.

Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques.

OBJECTIVES Therapeutic hypothermia (32-34 degrees C) is recommended for comatose survivors of cardiac arrest; however, the optimal technique for cooling is unknown. We aimed to compare therapeutic hypothermia using either surface or endovascular techniques in terms of efficacy, complications and outcome. DESIGN Retrospective cohort study. SETTING Thirty-bed teaching hospital intensive care unit (ICU). PATIENTS All patients (n=83) undergoing therapeutic hypothermia following cardiac arrest over a 2.5-year period. The mean age was 61+/-16 years; 88% of arrests occurred out of hospital, and 64% were ventricular fibrillation/tachycardia. INTERVENTIONS Therapeutic hypothermia was initiated in the ICU using iced Hartmanns solution, followed by either surface (n=41) or endovascular (n=42) cooling; choice of technique was based upon endovascular device availability. The target temperature was 32-34 degrees C for 12-24 h, followed by rewarming at a rate of 0.25 degrees Ch(-1). MEASUREMENTS AND MAIN RESULTS Endovascular cooling provided a longer time within the target temperature range (p=0.02), less temperature fluctuation (p=0.003), better control during rewarming (0.04), and a lower 48-h temperature load (p=0.008). Endovascular cooling also produced less cooling-associated complications in terms of both overcooling (p=0.05) and failure to reach the target temperature (p=0.04). After adjustment for known confounders, there were no differences in outcome between the groups in terms of ICU or hospital mortality, ventilator free days and neurological outcome. CONCLUSION Endovascular cooling provides better temperature management than surface cooling, as well as a more favorable complication profile. The equivalence in outcome suggested by this small study requires confirmation in a randomized trial.

Meta‐analysis of the association between preoperative anaemia and mortality after surgery

Numerous published studies have explored associations between anaemia and adverse outcomes after surgery. However, there are no evidence syntheses describing the impact of preoperative anaemia on postoperative outcomes.

Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care

RATIONALE Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level. OBJECTIVES To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use. METHODS Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses. MEASUREMENTS AND MAIN RESULTS Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs (

Frequency of surgical treatment and related hospital procedures in the UK: a national ecological study using hospital episode statistics

25,608 vs.

Intensive care utilization and outcomes after high-risk surgery in Scotland: a population-based cohort study

16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity. CONCLUSIONS This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society.

Perioperative myocardial injury in patients receiving cardiac output-guided haemodynamic therapy: a substudy of the OPTIMISE Trial

Background Despite evidence of high activity, the number of surgical procedures performed in UK hospitals, their cost and subsequent mortality remain unclear. Methods Time-trend ecological study using hospital episode data from England, Scotland, Wales and Northern Ireland. The primary outcome was the number of in-hospital procedures, grouped using three increasingly specific categories of surgery. Secondary outcomes were all-cause mortality, length of hospital stay and healthcare costs according to standard National Health Service tariffs. Results Between April 1, 2009 and March 31, 2014, 39 631 801 surgical patient episodes were recorded. There was an annual average of 7 926 360 procedures (inclusive category), 5 104 165 procedures (intermediate category) and 1 526 421 procedures (restrictive category). This equates to 12 537, 8073 and 2414 procedures per 100 000 population per year, respectively. On average there were 85 181 deaths (1.1%) within 30 days of a procedure each year, rising to 178 040 deaths (2.3%) after 90 days. Approximately 62.8% of all procedures were day cases. Median length of stay for in-patient procedures was 1.7 (1.3-2.0) days. The total cost of surgery over the 5 yr period was £54.6 billion (

Intensive Care after High-risk Surgery: What's in a Name?

104.4 billion), representing an average annual cost of £10.9 billion (inclusive), £9.5 billion (intermediate) and £5.6 billion (restrictive). For each category, the number of procedures increased each year, while mortality decreased. One-third of all mortalities in national death registers occurred within 90 days of a procedure (inclusive category). Conclusions The number of surgical procedures in the UK varies widely according to definition. The number of procedures is slowly increasing whilst the number of deaths is decreasing.

Which intravenous fluid for the surgical patient

Background. The optimal perioperative use of intensive care unit (ICU) resources is not yet defined. We sought to determine the effect of ICU admission on perioperative (30 day) and long-term mortality. Methods. This was an observational study of all surgical patients in Scotland during 2005–7 followed up until 2012. Patient, operative, and care process factors were extracted. The primary outcome was perioperative mortality; secondary outcomes were 1 and 4 yr mortality. Multivariable regression was used to construct a risk prediction model to allow standard-risk and high-risk groups to be defined based on deciles of predicted perioperative mortality risk, and to determine the effect of ICU admission (direct from theatre; indirect after initial care on ward; no ICU admission) on outcome adjusted for confounders. Results. There were 572 598 patients included. The risk model performed well (c-index 0.92). Perioperative mortality occurred in 1125 (0.2%) in the standard-risk group (n=510 979) and in 3636 (6.4%) in the high-risk group (n=56 785). Patients with no ICU admission within 7 days of surgery had the lowest perioperative mortality (whole cohort 0.7%; high-risk cohort 5.3%). Indirect ICU admission was associated with a higher risk of perioperative mortality when compared with direct admission for the whole cohort (20.9 vs 12.1%; adjusted odds ratio 2.39, 95% confidence interval 2.01–2.84; P<0.01) and for high-risk patients (26.2 vs 17.8%; adjusted odds ratio 1.64, 95% confidence interval 1.37–1.96; P<0.01). Compared with direct ICU admission, indirectly admitted patients had higher severity of illness on admission, required more organ support, and had an increased duration of ICU stay. Conclusions. Indirect ICU admission was associated with increased mortality and increased requirement for organ support. Trial registration. UKCRN registry no. 15761.