Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis.

BACKGROUND: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use. CONCLUSIONS: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Management of Patients on Preoperative Opioid Therapy.

Enhanced recovery pathways have quickly become part of the standard of care for patients undergoing elective surgery, especially in North America and Europe. One of the central tenets of this multidisciplinary approach is the use of multimodal analgesia with opioid-sparing and even opioid-free anesthesia and analgesia. However, the current state is a historically high use of opioids for both appropriate and inappropriate reasons, and patients with chronic opioid use before their surgery represent a common, often difficult-to-manage population for the enhanced recovery providers and health care team at large. Furthermore, limited evidence and few proven successful protocols exist to guide providers caring for these at-risk patients throughout their elective surgical experience. Therefore, the fourth Perioperative Quality Initiative brought together an international team of multidisciplinary experts, including anesthesiologists, nurse anesthetists, surgeons, pain specialists, neurologists, nurses, and other experts with the objective of providing consensus recommendations. Specifically, the goal of this consensus document is to minimize opioid-related complications by providing expert-based consensus recommendations that reflect the strength of the medical evidence regarding: (1) the definition, categorization, and risk stratification of patients receiving opioids before surgery; (2) optimal perioperative treatment strategies for patients receiving preoperative opioids; and (3) optimal discharge and continuity of care management practices for patients receiving opioids preoperatively. The overarching theme of this document is to provide health care providers with guidance to reduce potentially avoidable opioid-related complications including opioid dependence (both physical and behavioral), disability, and death. Enhanced recovery programs attempt to incorporate best practices into pathways of care. By presenting the available evidence for perioperative management of patients on opioids, this consensus panel hopes to encourage further development of pathways specific to this high-risk group to mitigate the often unintentional iatrogenic and untoward effects of opioids and to improve perioperative outcomes.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Opioid Minimization in Opioid-Naïve Patients.

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway.

Patient-reported outcomes (PROs) are measures of health status that come directly from the patient. PROs are an underutilized tool in the perioperative setting. Enhanced recovery pathways (ERPs) have primarily focused on traditional measures of health care quality such as complications and hospital length of stay. These measures do not capture postdischarge outcomes that are meaningful to patients such as function or freedom from disability. PROs can be used to facilitate shared decisions between patients and providers before surgery and establish benchmark recovery goals after surgery. PROs can also be utilized in quality improvement initiatives and clinical research studies. An expert panel, the Perioperative Quality Initiative (POQI) workgroup, conducted an extensive literature review to determine best practices for the incorporation of PROs in an ERP. This international group of experienced clinicians from North America and Europe met at Stony Brook, NY, on December 2-3, 2016, to review the evidence supporting the use of PROs in the context of surgical recovery. A modified Delphi method was used to capture the collective expertise of a diverse group to answer clinical questions. During 3 plenary sessions, the POQI PRO subgroup presented clinical questions based on a literature review, presented evidenced-based answers to those questions, and developed recommendations which represented a consensus opinion regarding the use of PROs in the context of an ERP. The POQI workgroup identified key criteria to evaluate patient-reported outcome measures (PROMs) for their incorporation in an ERP. The POQI workgroup agreed on the following recommendations: (1) PROMs in the perioperative setting should be collected in the framework of physical, mental, and social domains. (2) These data should be collected preoperatively at baseline, during the immediate postoperative time period, and after hospital discharge. (3) In the immediate postoperative setting, we recommend using the Quality of Recovery-15 score. After discharge at 30 and 90 days, we recommend the use of the World Health Organization Disability Assessment Scale 2.0, or a tailored use of the Patient-Reported Outcomes Measurement Information System. (4) Future study that consistently applies PROMs in an ERP will define the role these measures will have evaluating quality and guiding clinical care. Consensus guidelines regarding the incorporation of PRO measures in an ERP were created by the POQI workgroup. The inclusion of PROMs with traditional measures of health care quality after surgery provides an opportunity to improve clinical care.

Trial of the route of early nutritional support in critically ill adults.

BACKGROUND: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS: We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS: We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS: We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).

Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures.

BACKGROUND: Perioperative fluid strategies influence clinical outcomes following major surgery. Many intravenous fluid preparations are based on simple solutions, such as normal saline, that feature an electrolyte composition that differs from that of physiological plasma. Buffered fluids have a theoretical advantage of containing a substrate that acts to maintain the body's acid-base status - typically a bicarbonate or a bicarbonate precursor such as maleate, gluconate, lactate, or acetate. Buffered fluids also provide additional electrolytes, including potassium, magnesium, and calcium, more closely matching the electrolyte balance of plasma. The putative benefits of buffered fluids have been compared with those of non-buffered fluids in the context of clinical studies conducted during the perioperative period. This review was published in 2012, and was updated in 2017. OBJECTIVES: To review effects of perioperative intravenous administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance, or both, on clinical outcomes in adults undergoing all types of surgery. SEARCH METHODS: We electronically searched the Clinicaltrials.gov major trials registry, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 6) in the Cochrane Library, MEDLINE (1966 to June 2016), Embase (1980 to June 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to June 2016). We handsearched conference abstracts and, when possible, contacted leaders in the field. We reran the search in May 2017. We added one potential new study of interest to the list of 'Studies awaiting classification' and will incorporate this trial into formal review findings when we prepare the review update. SELECTION CRITERIA: Only randomized controlled trials that compared buffered versus non-buffered intravenous fluids for surgical patients were eligible for inclusion. We excluded other forms of comparison such as crystalloids versus colloids and colloids versus different colloids. DATA COLLECTION AND ANALYSIS: Two review authors screened references for eligibility, extracted data, and assessed risks of bias. We resolved disagreements by discussion and consensus, in collaboration with a third review author. We contacted trial authors to request additional information when appropriate. We presented pooled estimates for dichotomous outcomes as odds ratios (ORs) and for continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We analysed data via Review Manager 5.3 using fixed-effect models, and when heterogeneity was high (I² > 40%), we used random-effects models. MAIN RESULTS: This review includes, in total, 19 publications of 18 randomized controlled trials with a total of 1096 participants. We incorporated five of those 19 studies (330 participants) after the June 2016 update. Outcome measures in the included studies were thematically similar, covering perioperative electrolyte status, renal function, and acid-base status; however, we found significant clinical and statistical heterogeneity among the included studies. We identified variable protocols for fluid administration and total volumes of fluid administered to patients intraoperatively. Trial authors variably reported outcome data at disparate time points and with heterogeneous patient groups. Consequently, many outcome measures are reported in small group sizes, reducing overall confidence in effect size, despite relatively low inherent bias in the included studies. Several studies reported orphan outcome measures. We did not include in the results of this review one large, ongoing study of saline versus Ringer's solution.We found insufficient evidence on effects of fluid therapies on mortality and postoperative organ dysfunction (defined as renal insufficiency leading to renal replacement therapy); confidence intervals were wide and included both clinically relevant benefit and harm: mortality (Peto OR 1.85, 95% CI 0.37 to 9.33; I² = 0%; 3 trials, 6 deaths, 276 participants; low-quality evidence); renal insufficiency (OR 0.82, 95% CI 0.34 to 1.98; I² = 0%; 4 trials, 22 events, 276 participants; low-quality evidence).We noted several metabolic differences, including a difference in postoperative pH measured at end of surgery of 0.05 units - lower in the non-buffered fluid group (12 studies with a total of 720 participants; 95% CI 0.04 to 0.07; I² = 61%). However, this difference was not maintained on postoperative day one. We rated the quality of evidence for this outcome as moderate. We observed a higher postoperative serum chloride level immediately after operation, with use of non-buffered fluids reported in 10 studies with a total of 530 participants (MD 6.77 mmol/L, 95% CI 3.38 to 10.17), and this difference persisted until day one postoperatively (five studies with a total of 258 participants; MD 8.48 mmol/L, 95% CI 1.08 to 15.88). We rated the quality of evidence for this outcome as moderate. AUTHORS' CONCLUSIONS: Current evidence is insufficient to show effects of perioperative administration of buffered versus non-buffered crystalloid fluids on mortality and organ system function in adult patients following surgery. Benefits of buffered fluid were measurable in biochemical terms, particularly a significant reduction in postoperative hyperchloraemia and metabolic acidosis. Small effect sizes for biochemical outcomes and lack of correlated clinical follow-up data mean that robust conclusions on major morbidity and mortality associated with buffered versus non-buffered perioperative fluid choices are still lacking. Larger studies are needed to assess these relevant clinical outcomes.

Metabolic dysfunction in lymphocytes promotes postoperative morbidity.

Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61-82 years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (≤1.3 x 10(9)·l(-1); <20% white cell count; prevalence 15-18%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1-2.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26-65%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1ß in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic patients and/or acquired postoperatively increases the risk of postoperative infection through glucocorticoid activation of caspase-1 via the NLRP1 inflammasome.

Does gastric tonometry-guided therapy reduce total mortality in critically ill patients?

Zhang and colleagues have recently published a systematic review and meta-analysis of six studies and conclude that 'gastric tonometry guided therapy can reduce total mortality in critically ill patients'. So why did gastric tonometry come and go, and what can we learn from this piece of modern history?

Detecting acute distress and risk of future psychological morbidity in critically ill patients: validation of the intensive care psychological assessment tool.

INTRODUCTION: The psychological impact of critical illness on a patient can be severe, and frequently results in acute distress as well as psychological morbidity after leaving hospital. A UK guideline states that patients should be assessed in critical care units, both for acute distress and risk of future psychological morbidity; but no suitable method for carrying out this assessment exists. The Intensive care psychological assessment tool (IPAT) was developed as a simple, quick screening tool to be used routinely to detect acute distress, and the risk of future psychological morbidity, in critical care units. METHODS: A validation study of IPAT was conducted in the critical care unit of a London hospital. Once un-sedated, orientated and alert, critical care patients were assessed with the IPAT and validated tools for distress, to determine the IPAT's concurrent validity. Fifty six patients took IPAT again to establish test-retest reliability. Finally, patients completed posttraumatic stress disorder (PTSD), depression and anxiety questionnaires at three months, to determine predictive validity of the IPAT. RESULTS: One hundred and sixty six patients completed the IPAT, and 106 completed follow-up questionnaires at 3 months. Scale analysis showed IPAT was a reliable 10-item measure of critical care-related psychological distress. Test-retest reliability was good (r =0.8). There was good concurrent validity with measures of anxiety and depression (r =0.7, P <0.01; r =0.6, P <0.01). With a cut-point of ≥7, the IPAT had 82% sensitivity and 65% specificity to detect concurrent anxiety; and 80% sensitivity and 66% specificity to detect concurrent low mood (area under the curve (AUC) =0.8 for both). Predictive validity for psychological morbidity was good (r =0.4, P <0.01; r =0.64, P <0.01 for PTSD with days 1 and 2 data). The IPAT had 69% specificity and 57% sensitivity to predict future psychological morbidity (AUC =0.7). CONCLUSIONS: The IPAT was found to have good reliability and validity. Sensitivity and specificity analysis suggest the IPAT could provide a way of allowing staff to assess psychological distress among critical care patients after further replication and validation. Further work is also needed to determine its utility in predicting future psychological morbidity.

Risk stratification tools for predicting morbidity and mortality in adult patients undergoing major surgery: qualitative systematic review.

Risk stratification is essential for both clinical risk prediction and comparative audit. There are a variety of risk stratification tools available for use in major noncardiac surgery, but their discrimination and calibration have not previously been systematically reviewed in heterogeneous patient cohorts.Embase, MEDLINE, and Web of Science were searched for studies published between January 1, 1980 and August 6, 2011 in adult patients undergoing major noncardiac, nonneurological surgery. Twenty-seven studies evaluating 34 risk stratification tools were identified which met inclusion criteria. The Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality and the Surgical Risk Scale were demonstrated to be the most consistently accurate tools that have been validated in multiple studies; however, both have limitations. Future work should focus on further evaluation of these and other parsimonious risk predictors, including validation in international cohorts. There is also a need for studies examining the impact that the use of these tools has on clinical decision making and patient outcome.

Should hydroxyethyl starch solutions be totally banned?

The choice of which intravenous solution to prescribe remains a matter of considerable debate in intensive care units around the world. Trends have been moving away from using hydroxyethyl starch solutions following concerns about safety. But are the available data sufficient to clearly assess the risk-benefit balance for all patients, and is there enough evidence of harm to justify removing these drugs completely from our hospitals?

Restrictive versus conventional ward fluid therapy in non-cardiac surgery patients and the effect on postoperative complications: a meta-analysis.

BACKGROUND: Diligent fluid management is an instrumental part of Enhanced Recovery After Surgery. However, the effect of a ward regimen to limit intravenous fluid administration on outcome remains unclear. We performed a meta-analysis investigating the effect of a restrictive versus a conventional fluid regimen on complications in patients after non-cardiac surgery in the postoperative period on the clinical ward. STUDY DESIGN: We performed a systematic search in MEDLINE, Embase, Cochrane Library, and CINAHL databases, from the start of indexing until June 2022, with constraints for English language and adult human study participants. Data were combined using classic methods of meta-analyses and were expressed as weighted pooled risk ratio (RR) or odds ratio (OR) with 95% confidence interval (CI). Quality assessment and risk of bias analyses was performed according to PRISMA guidelines. RESULTS: Seven records, three randomized controlled trials, and four non-randomized studies were included with a total of 883 patients. A restrictive fluid regimen was associated with a reduction in overall complication rate in the RCTs (RR 0.46, 95% CI 0.23 to 0.95; P < .03; I2 = 35%). This reduction in overall complication rate was not consistent in the non-randomized studies (RR 0.74, 95% CI 0.53 to 1.03; P 0.07; I2 = 45%). No significant association was found for mortality using a restrictive fluid regimen (RCTs OR 0.51, 95% CI 0.05 to 4.90; P = 0.56; I2 = 0%, non-randomized studies OR 0.30, 95% CI 0.06 to 1.46; P = 0.14; I2 = 0%). A restrictive fluid regimen is significantly associated with a reduction in postoperative length of stay in the non-randomized studies (MD - 1.81 days, 95% CI - 3.27 to - 0.35; P = 0.01; I2 = 0%) but not in the RCTs (MD 0.60 days, 95% CI - 0.75 to 1.95; P = 0.38). Risk of bias was moderate to high. Methodological quality was very low to moderate. CONCLUSION: This meta-analysis suggests restrictive fluid therapy on the ward may be associated with an effect on postoperative complication rate. However, the quality of evidence was moderate to low, the sample size was small, and the data came from both RCTs and non-randomized studies.

Enhanced recovery pathways as a way to reduce surgical morbidity.

PURPOSE OF REVIEW: The aim of this review is to summarize important publications in enhanced recovery during 2010-2011 and to highlight key themes. Specifically, we focus on updated systematic reviews of high-quality clinical trials of enhanced recovery in colorectal surgery, exemplar studies of enhanced recovery in other specialties, and exploration of which elements of the enhanced recovery package might be associated with improved patient outcome. RECENT FINDINGS: An expanding evidence base of clinical trials and implementation evaluations supports the effectiveness of enhanced recovery programmes in improving outcome following major elective surgery. The majority of this literature derives from the study of patients undergoing colorectal surgery, but increasingly enhanced recovery is spreading to other surgical specialties. The combination of reduced length of hospital stay (a surrogate for morbidity) with no increase in readmissions to hospital suggests that morbidity is reduced with enhanced recovery. Inconsistency in morbidity reporting limits the value of pooling data between studies, but within study comparisons in general support this conclusion. Patients adhering to an enhanced recovery programme return to normal function faster than those following traditional care pathways. SUMMARY: Enhanced recovery adoption is likely to continue to grow (range of specialties and penetration within specialties). This progression is supported by the available published data.

Investigating risk factors for psychological morbidity three months after intensive care: a prospective cohort study.

INTRODUCTION: There is growing evidence of poor mental health and quality of life among survivors of intensive care. However, it is not yet clear to what extent the trauma of life-threatening illness, associated drugs and treatments, or patients' psychological reactions during intensive care contribute to poor psychosocial outcomes. Our aim was to investigate the relative contributions of a broader set of risk factors and outcomes than had previously been considered in a single study. METHODS: A prospective cohort study of 157 mixed-diagnosis highest acuity patients was conducted in a large general intensive care unit (ICU). Data on four groups of risk factors (clinical, acute psychological, socio-demographic and chronic health) were collected during ICU admissions. Post-traumatic stress disorder (PTSD), depression, anxiety and quality of life were assessed using validated questionnaires at three months (n = 100). Multivariable analysis was used. RESULTS: At follow-up, 55% of patients had psychological morbidity: 27.1% (95% CI: 18.3%, 35.9%) had probable PTSD; 46.3% (95% CI: 36.5%, 56.1%) probable depression, and 44.4% (95% CI: 34.6%, 54.2%) anxiety. The strongest clinical risk factor for PTSD was longer duration of sedation (regression coefficient = 0.69 points (95% CI: 0.12, 1.27) per day, scale = 0 to 51). There was a strong association between depression at three months and receiving benzodiazepines in the ICU (mean difference between groups = 6.73 points (95% CI: 1.42, 12.06), scale = 0 to 60). Use of inotropes or vasopressors was correlated with anxiety, and corticosteroids with better physical quality of life. CONCLUSIONS: Strikingly high rates of psychological morbidity were found in this cohort of intensive care survivors. The study's key finding was that acute psychological reactions in the ICU were the strongest modifiable risk factors for developing mental illness in the future. The observation that use of different ICU drugs correlated with different psychological outcomes merits further investigation. These findings suggest that psychological interventions, along with pharmacological modifications, could help reduce poor outcomes, including PTSD, after intensive care.

Perioperative increase in global blood flow to explicit defined goals and outcomes following surgery.

BACKGROUND: Studies have suggested that increasing whole body blood flow and oxygen delivery around the time of surgery reduces mortality, morbidity and the expense of major operations. OBJECTIVES: To describe the effects of increasing perioperative blood flow using fluids with or without inotropes or vasoactive drugs. Outcomes were mortality, morbidity, resource utilization and health status. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2012, Issue 1), MEDLINE (1966 to March 2012) and EMBASE (1982 to March 2012). We manually searched the proceedings of major conferences and personal reference databases up to December 2011. We contacted experts in the field and pharmaceutical companies for published and unpublished data. SELECTION CRITERIA: We included randomized controlled trials with or without blinding. We included studies involving adult patients (aged 16 years or older) undergoing surgery (patients having a procedure in an operating room). The intervention met the following criteria. 'Perioperative' was defined as starting up to 24 hours before surgery and stopping up to six hours after surgery. 'Targeted to increase global blood flow' was defined by explicit measured goals that were greater than in controls, specifically one or more of cardiac index, oxygen delivery, oxygen consumption, stroke volume (and the respective derived indices), mixed venous oxygen saturation (SVO(2)), oxygen extraction ratio (0(2)ER) or lactate. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. We contacted study authors for additional data. We used Review Manager software. MAIN RESULTS: We included 31 studies of 5292 participants. There was no difference in mortality: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI 0.76 to 1.05, P = 0.18). However, the results were sensitive to analytical methods and the intervention was better than control when inverse variance or Mantel-Haenszel random-effects models were used, RR of 0.72 (95% CI 0.55 to 0.95, P = 0.02). The results were also sensitive to withdrawal of studies with methodological limitations. The rates of three morbidities were reduced by increasing global blood flow: renal failure, RR of 0.71 (95% CI 0.57 to 0.90); respiratory failure, RR of 0.51 (95% CI 0.28 to 0.93); and wound infections, RR of 0.65 (95% CI 0.51 to 0.84). There were no differences in the rates of nine other morbidities: arrhythmia, pneumonia, sepsis, abdominal infection, urinary tract infection, myocardial infarction, congestive cardiac failure or pulmonary oedema, or venous thrombosis. The number of patients with complications was reduced by the intervention, RR of 0.68 (95% CI 0.58 to 0.80). Hospital length of stay was reduced in the treatment group by a mean of 1.16 days (95% CI 0.43 to 1.89, P = 0.002). There was no difference in critical care length of stay. There were insufficient data to comment on quality of life and cost effectiveness. AUTHORS' CONCLUSIONS: It remains uncertain whether increasing blood flow using fluids, with or without inotropes or vasoactive drugs, reduces mortality in adults undergoing surgery. The primary analysis in this review (mortality at longest follow-up) showed no difference between the intervention and control, but this result was sensitive to the method of analysis, the withdrawal of studies with methodological limitations, and is dominated by a single large RCT. Overall, for every 100 patients in whom blood flow is increased perioperatively to defined goals, one can expect 13 in 100 patients (from 40/100 to 27/100) to avoid a complication, 2/100 to avoid renal impairment (from 8/100 to 6/100), 5/100 to avoid respiratory failure (from 10/100 to 5/100), and 4/100 to avoid postoperative wound infection (from 10/100 to 6/100). On average, patients receiving the intervention stay in hospital one day less. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.

Perioperative buffered versus non-buffered fluid administration for surgery in adults.

BACKGROUND: Perioperative fluid therapy influences clinical outcomes following major surgery. Fluid preparations may be based on a simple non-buffered salt solution, such as normal saline, or may be modified with bicarbonate or bicarbonate precursor buffers, such as maleate, gluconate, lactate or acetate, to better reflect the human physiological state. These latter fluids have theoretical advantages over normal saline in preventing hyperchloraemic acidosis. A number of clinical studies have now compared fluid preparations with and without a buffer to achieve a balanced electrolyte solution for perioperative fluid resuscitation. OBJECTIVES: To review the safety and efficacy of perioperative administration of buffered versus non-buffered fluids for plasma volume expansion or maintenance in adult patients undergoing surgery. SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and CINAHL (1982 to May 2011). We handsearched conference abstracts and where possible, contacted leaders in the field. SELECTION CRITERIA: We only included randomized trials of buffered versus non-buffered intravenous fluids for perioperative fluid resuscitation. The trials with other forms of comparisons such as crystalloids versus colloids and colloids versus different colloids were excluded. We also excluded trials using hypertonic fluids and dextrose-based fluids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of clinical trials. We resolved any disagreements by discussion. We contacted the trial authors to provide additional information where appropriate. We presented pooled estimates of the dichotomous outcomes as odds ratios (OR) and on continuous outcomes as mean differences, with 95% confidence intervals (CI). We analysed data on Review Manager 5.1 using fixed-effect models, and when heterogeneity was high (I² > 40%) random-effect models were used. MAIN RESULTS: We identified 14 publications reporting 13 trials or comparisons with a total of 706 participants. For many of the outcomes reported, there was significant clinical and statistical heterogeneity. The primary outcome of mortality at any time was reported in only three studies with a total of 267 patients. The mortality rate was 2.9% for the buffered fluids group and 1.5% for the non-buffered fluids group but this difference was not statistically significant. The Peto OR was 1.85 (95% CI 0.37 to 9.33, P = 0.45, I(2)= 0%). Organ dysfunction was only presented for renal impairment. There was no difference in renal insufficiency leading to renal replacement therapy between the buffered and non-buffered groups (OR 0.61, 95% CI 0.23 to 1.63, P = 0.32, I(2) = 0%). Markers of organ system failure as assessed by urine output, creatinine and its variables (for renal function), PaC0(2) (respiratory function) and postoperative nausea and vomiting (gastro-intestinal function) showed a statistically significant difference only in PaC0(2) levels. The mean difference was 1.18 with lower PaC0(2) levels in the non-buffered fluid group (95% CI 0.09 to 2.28, P = 0.03, I(2) = 0%) compared to the buffered fluid group.There was no difference in intraoperative blood loss nor the volumes of intraoperative red cell or fresh frozen plasma transfused between groups. There was an increase in platelet transfusion in the non-buffered group which was statistically significant after analysing the transformed data (log transformation because the data were highly skewed).A number of metabolic differences were noted. There was a difference in postoperative pH of 0.06 units, lower in the non-buffered fluid group (95% CI 0.04 to 0.08, P < 0.00001, I(2) = 74%). However, this difference was not maintained on postoperative day one. The non-buffered fluid group also had significantly greater base deficit, serum sodium and chloride levels.There was no difference demonstrated in length of hospital stay and no data were reported on cost or quality of life. AUTHORS' CONCLUSIONS: The administration of buffered fluids to adult patients during surgery is equally safe and effective as the administration of non-buffered saline-based fluids. The use of buffered fluids is associated with less metabolic derangement, in particular hyperchloraemia and metabolic acidosis. Larger studies are needed to assess robust outcomes such as mortality.