Michael P. W. Grocott

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.

Perioperative fluid management and clinical outcomes in adults

The administration of IV fluid to avoid dehydration, maintain an effective circulating volume, and prevent inadequate tissue perfusion should be considered, along with the maintenance of sleep, pain relief, and muscular relaxation, a core element of the perioperative practice of anesthesia. Knowledge of the effects of different fluids has increased in recent years, and the choice of fluid type in a variety of clinical situations can now be rationally guided by an understanding of the physicochemical and biological properties of the various crystalloid and colloid solutions available. However, there are few useful clinical outcome data to guide this decision. Deciding how much fluid to give has historically been more controversial than choosing which fluid to use. A number of clinical studies support the notion that an approach based on administering fluids to achieve maximal left ventricular stroke volume (while avoiding excess fluid administration and consequent impairment of left ventricular performance) may improve outcomes. In this article, we review the available fluid types and strategies of fluid administration and discuss their relationship to clinical outcomes in adults.

Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest

BACKGROUND The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest. METHODS We obtained samples of arterial blood from 10 climbers during their ascent to and descent from the summit of Mount Everest. The partial pressures of arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)), pH, and hemoglobin and lactate concentrations were measured. The arterial oxygen saturation (SaO(2)), bicarbonate concentration, base excess, and alveolar-arterial oxygen difference were calculated. RESULTS PaO(2) fell with increasing altitude, whereas SaO(2) was relatively stable. The hemoglobin concentration increased such that the oxygen content of arterial blood was maintained at or above sea-level values until the climbers reached an elevation of 7100 m (23,294 ft). In four samples taken at 8400 m (27,559 ft)--at which altitude the barometric pressure was 272 mm Hg (36.3 kPa)--the mean PaO(2) in subjects breathing ambient air was 24.6 mm Hg (3.28 kPa), with a range of 19.1 to 29.5 mm Hg (2.55 to 3.93 kPa). The mean PaCO(2) was 13.3 mm Hg (1.77 kPa), with a range of 10.3 to 15.7 mm Hg (1.37 to 2.09 kPa). At 8400 m, the mean arterial oxygen content was 26% lower than it was at 7100 m (145.8 ml per liter as compared with 197.1 ml per liter). The mean calculated alveolar-arterial oxygen difference was 5.4 mm Hg (0.72 kPa). CONCLUSIONS The elevated alveolar-arterial oxygen difference that is seen in subjects who are in conditions of extreme hypoxia may represent a degree of subclinical high-altitude pulmonary edema or a functional limitation in pulmonary diffusion.

Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study

Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n = 24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2 = 12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n = 7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.

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.

Comparison of P-POSSUM risk-adjusted mortality rates after surgery between patients in the USA and the UK

The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) criteria have been used to assess surgical risk in patients in the UK. The aim was to determine how applicable these criteria are to patients undergoing surgery in the USA.

Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study

BACKGROUND Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake [Formula: see text] at lactate threshold ([Formula: see text]) in such patients. METHODS We prospectively studied 39 consecutive subjects (27 males) with T3-4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in [Formula: see text] at [Formula: see text] over time and between the groups were compared using a compound symmetry covariance linear mixed model. RESULTS Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline [age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality]. In all subjects, [Formula: see text] at [Formula: see text] significantly reduced between baseline and week 0 [-1.9 ml kg(-1) min(-1); 95% confidence interval (CI) -1.3, -2.6; P<0.0001]. In the exercise group, [Formula: see text] at [Formula: see text] significantly improved between week 0 and week 6 (+2.1 ml kg(-1) min(-1); 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (-0.7 ml kg(-1) min(-1); 95% CI -1.66, +0.37; P=0.204). CONCLUSIONS NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks. CLINICAL TRIAL REGISTRATION NCT 01325909.

Oxygen therapy in critical illness: precise control of arterial oxygenation and permissive hypoxemia.

Objective:The management of hypoxemia in critically ill patients is challenging. Whilst the harms of tissue hypoxia are well recognized, the possibility of harm from excess oxygen administration, or other interventions targeted at mitigating hypoxemia, may be inadequately appreciated. The benefits of attempting to fully reverse arterial hypoxemia may be outweighed by the harms associated with high concentrations of supplemental oxygen and invasive mechanical ventilation strategies. We propose two novel related strategies for the management of hypoxemia in critically ill patients. First, we describe precise control of arterial oxygenation involving the specific targeting of arterial partial pressure of oxygen or arterial hemoglobin oxygen saturation to individualized target values, with the avoidance of significant variation from these levels. The aim of precise control of arterial oxygenation is to avoid the harms associated with inadvertent hyperoxia or hypoxia through careful and precise control of arterial oxygen levels. Secondly, we describe permissive hypoxemia: the acceptance of levels of arterial oxygenation lower than is conventionally tolerated in patients. The aim of permissive hypoxemia is to minimize the possible harms caused by restoration of normoxemia while avoiding tissue hypoxia. This review sets out to discuss the strengths and limitations of precise control of arterial oxygenation and permissive hypoxemia as candidate management strategies in hypoxemic critically ill patients. Design:We searched PubMed for references to “permissive hypoxemia/hypoxaemia” and “precise control of arterial oxygenation” as well as reference to “profound hypoxemia/hypoxaemia/hypoxia,” “severe hypoxemia/hypoxaemia/hypoxia.” We searched personal reference libraries in the areas of critical illness and high altitude physiology and medicine. We also identified large clinical studies in patients with critical illness characterized by hypoxemia such as acute respiratory distress syndrome. Subjects:Studies were selected that explored the physiology of hypoxemia in healthy volunteers or critically ill patients. Setting:The data were subjectively assessed and combined to generate the narrative. Results:Inadequate tissue oxygenation and excessive oxygen administration can be detrimental to outcome but safety thresholds lack definition in critically ill patients. Precise control of arterial oxygenation provides a rational approach to the management of arterial oxygenation that reflects recent clinical developments in other settings. Permissive hypoxemia is a concept that is untested clinically and requires robust investigation prior to consideration of implementation. Both strategies will require accurate monitoring of oxygen administration and arterial oxygenation. Effective, reliable measurement of tissue oxygenation along with the use of selected biomarkers to identify suitable candidates and monitor harm will aid the development of permissive hypoxemia as viable clinical strategy. Conclusions:Implementation of precise control of arterial oxygenation may avoid the harms associated with excessive and inadequate oxygenation. However, at present there is no direct evidence to support the immediate implementation of permissive hypoxemia and a comprehensive evaluation of its value in critically ill patients should be a high research priority.

Perioperative increase in global blood flow to explicit defined goals and outcomes after surgery: a Cochrane Systematic Review

This systematic review and meta-analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults. We included randomized controlled trials of adult patients (aged 16 years or older) undergoing surgery. We included 31 studies of 5292 participants. There was no difference in mortality at the longest follow-up: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI: 0.76-1.05; P=0.18). However, the results were sensitive to analytical methods and withdrawal of studies with methodological limitations. The intervention reduced the rate of three morbidities (renal failure, respiratory failure, and wound infections) but not the rates of arrhythmia, myocardial infarction, congestive cardiac failure, venous thrombosis, and other types of infections. The number of patients with complications was also reduced by the intervention. Hospital length of stay was reduced in the treatment group by 1.16 days. There was no difference in critical care length of stay. The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis, withdrawal of studies with methodological limitations, and was dominated by a single large study. Patients receiving this intervention stayed in hospital 1 day less with fewer complications. 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.

High-altitude physiology and pathophysiology: implications and relevance for intensive care medicine

Cellular hypoxia is a fundamental mechanism of injury in the critically ill. The study of human responses to hypoxia occurring as a consequence of hypobaria defines the fields of high-altitude medicine and physiology. A new paradigm suggests that the physiological and pathophysiological responses to extreme environmental challenges (for example, hypobaric hypoxia, hyper-baria, microgravity, cold, heat) may be similar to responses seen in critical illness. The present review explores the idea that human responses to the hypoxia of high altitude may be used as a means of exploring elements of the pathophysiology of critical illness.