Why women are not small men: sex-related differences in perioperative cardiopulmonary exercise testing.

BACKGROUND: The use of preoperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative outcomes is increasingly prevalent. CPET-derived information enables personalised perioperative care and enhances shared decision-making. Sex-related differences in physical fitness are reported in non-perioperative literature. However, little attention has been paid to sex-related differences in the context of perioperative CPET. AIM: We explored differences in the physical fitness variables reported in a recently published multi-centre study investigating CPET before colorectal surgery. We also report the inclusion rate of females in published perioperative CPET cohorts that are shaping guidelines and clinical practice. METHODS: We performed a post hoc analysis of the trial data of 703 patients who underwent CPET prior to major elective colorectal surgery. We also summarised the female inclusion rate in peer-reviewed published reports of perioperative CPET. RESULTS: Fitness assessed using commonly used perioperative CPET variables-oxygen consumption at anaerobic threshold (AT) and peak exercise-was significantly higher in males than in females both before and after correction for body weight. In studies contributing to the development of perioperative CPET, 68.5% of the participants were male. CONCLUSION: To our knowledge, this is the first study to describe differences between males and females in CPET variables used in a perioperative setting. Furthermore, there is a substantial difference between the inclusion rates of males and females in this field. These findings require validation in larger cohorts and may have significant implications for both sexes in the application of CPET in the perioperative setting.

Arterial pulse pressure and postoperative morbidity in high-risk surgical patients.

BACKGROUND: Systemic arterial pulse pressure (systolic minus diastolic pressure) ≤53 mm Hg in patients with cardiac failure is correlated with reduced stroke volume and is independently associated with accelerated morbidity and mortality. Given that deconditioned surgical and heart failure patients share similar cardiopulmonary physiology, we examined whether lower pulse pressure is associated with excess morbidity after major surgery. METHODS: This was a prospective observational cohort study of patients deemed by their preoperative assessors to be at higher risk of postoperative morbidity. Preoperative pulse pressure was calculated before cardiopulmonary exercise testing. The primary outcome was any morbidity (PostOperative Morbidity Survey) occurring within 5 days of surgery, stratified by pulse pressure threshold ≤53 mm Hg. The relationship between pulse pressure, postoperative morbidity, and oxygen pulse (a robust surrogate for left ventricular stroke volume) was examined using logistic regression analysis (accounting for age, sex, BMI, cardiometabolic co-morbidity, and operation type). RESULTS: The primary outcome occurred in 578/660 (87.6%) patients, but postoperative morbidity was more common in 243/ 660 patients with preoperative pulse pressure ≤53 mm Hg{odds ratio (OR): 2.24 [95% confidence interval (CI): 1.29-3.38]; P<0.001). Pulse pressure ≤53 mm Hg [OR:1.23 (95% CI: 1.03-1.46); P=0.02] and type of surgery were independently associated with all-cause postoperative morbidity (multivariate analysis). Oxygen pulse <90% of population-predicted normal values was associated with pulse pressure ≤ 53 mm Hg [OR: 1.93 (95% CI: 1.32-2.84); P=0.007]. CONCLUSIONS: In deconditioned surgical patients, lower preoperative systemic arterial pulse pressure is associated with excess morbidity. These data are strikingly similar to meta-analyses identifying low pulse pressure as an independent risk factor for adverse outcomes in cardiac failure. Low preoperative pulse pressure is a readily available measure, indicating that detailed physiological assessment may be warranted. CLINICAL TRIAL REGISTRATION: ISRCT registry, ISRCTN88456378.

Comparison of risk-scoring systems in the prediction of outcome after liver resection.

BACKGROUND: Risk prediction techniques commonly used in liver surgery include the American Society of Anesthesiologists (ASA) grading, Charlson Comorbidity Index (CCI) and cardiopulmonary exercise tests (CPET). This study compares the utility of these techniques along with the number of segments resected as predictive tools in liver surgery. METHODS: A review of a unit database of patients undergoing liver resection between February 2008 and January 2015 was undertaken. Patient demographics, ASA, CCI and CPET variables were recorded along with resection size. Clavien-Dindo grade III-V complications were used as a composite outcome in analyses. Association between predictive variables and outcome was assessed by univariate and multivariate techniques. RESULTS: One hundred and seventy-two resections in 168 patients were identified. Grade III-V complications occurred after 42 (24.4%) liver resections. In univariate analysis of CPET variables, ventilatory equivalents for CO2 (VEqCO2) was associated with outcome. CCI score, but not ASA grade, was also associated with outcome. In multivariate analysis, the odds ratio of developing grade III-V complications for incremental increases in VEqCO2, CCI and number of liver segments resected were 1.09, 1.49 and 2.94, respectively. CONCLUSIONS: Of the techniques evaluated, resection size provides the simplest and most discriminating predictor of significant complications following liver surgery.

Elevated preoperative heart rate is associated with cardiopulmonary and autonomic impairment in high-risk surgical patients.

BACKGROUND: Elevated preoperative heart rate (HR) is associated with perioperative myocardial injury and death. In apparently healthy individuals, high resting HR is associated with development of cardiac failure. Given that patients with overt cardiac failure have poor perioperative outcomes, we hypothesized that subclinical cardiac failure, identified by cardiopulmonary exercise testing, was associated with elevated preoperative HR > 87 beats min -1 (HR > 87). METHODS: This was a secondary analysis of an observational cohort study of surgical patients aged ≥45 yr. The exposure of interest was HR > 87, recorded at rest before preoperative cardiopulmonary exercise testing. The predefined outcome measures were the following established predictors of mortality in patients with overt cardiac failure in the general population: ventilatory equivalent for carbon dioxide ( V˙E/V˙co2 ) ratio ≥34, heart rate recovery ≤6 and peak oxygen uptake ( V˙o2 ) ≤14 ml kg -1  min -1 . We used logistic regression analysis to test for association between HR > 87 and markers of cardiac failure. We also examined the relationship between HR > 87 and preoperative left ventricular stroke volume in a separate cohort of patients. RESULTS: HR > 87 was present in 399/1250 (32%) patients, of whom 438/1250 (35%) had V˙E/V˙co2 ratio ≥34, 200/1250 (16%) had heart rate recovery ≤6, and 396/1250 (32%) had peak V˙o2 ≤14 ml kg -1  min -1 . HR > 87 was independently associated with peak V˙o2 ≤14 ml kg -1  min -1 {odds ratio (OR) 1.69 [1.12-3.55]; P =0.01} and heart rate recovery ≤6 (OR 2.02 [1.30-3.14]; P <0.01). However, HR > 87 was not associated with V˙E/V˙co2 ratio ≥34 (OR 1.31 [0.92-1.87]; P =0.14). In a separate cohort, HR > 87 (33/181; 18.5%) was associated with impaired preoperative stroke volume (OR 3.21 [1.26-8.20]; P =0.01). CONCLUSIONS: Elevated preoperative heart rate is associated with impaired cardiopulmonary performance consistent with clinically unsuspected, subclinical cardiac failure. CLINICAL TRIAL REGISTRATION: ISRCTN88456378.

Validation of preoperative cardiopulmonary exercise testing-derived variables to predict in-hospital morbidity after major colorectal surgery.

BACKGROUND: In single-centre studies, postoperative complications are associated with reduced fitness. This study explored the relationship between cardiorespiratory fitness variables derived by cardiopulmonary exercise testing (CPET) and in-hospital morbidity after major elective colorectal surgery. METHODS: Patients underwent preoperative CPET with recording of in-hospital morbidity. Receiver operating characteristic (ROC) curves and logistic regression were used to assess the relationship between CPET variables and postoperative morbidity. RESULTS: Seven hundred and three patients from six centres in the UK were available for analysis (428 men, 275 women). ROC curve analysis of oxygen uptake at estimated lactate threshold (V˙o2 at θ^L ) and at peak exercise (V˙o2peak ) gave an area under the ROC curve (AUROC) of 0·79 (95 per cent c.i. 0·76 to 0·83; P < 0·001; cut-off 11·1 ml per kg per min) and 0·77 (0·72 to 0·82; P < 0·001; cut-off 18·2 ml per kg per min) respectively, indicating that they can identify patients at risk of postoperative morbidity. In a multivariable logistic regression model, selected CPET variables and body mass index (BMI) were associated significantly with increased odds of in-hospital morbidity (V˙o2 at θ^L 11·1 ml per kg per min or less: odds ratio (OR) 7·56, 95 per cent c.i. 4·44 to 12·86, P < 0·001; V˙o2peak 18·2 ml per kg per min or less: OR 2·15, 1·01 to 4·57, P = 0·047; ventilatory equivalents for carbon dioxide at estimated lactate threshold (V˙E /V˙co2 at θ^L ) more than 30·9: OR 1·38, 1·00 to 1·89, P = 0·047); BMI exceeding 27 kg/m2 : OR 1·05, 1·03 to 1·08, P < 0·001). A laparoscopic procedure was associated with a decreased odds of complications (OR 0·30, 0·02 to 0·44; P = 0·033). This model was able to discriminate between patients with, and without in-hospital morbidity (AUROC 0·83, 95 per cent c.i. 0·79 to 0·87). No adverse clinical events occurred during CPET across the six centres. CONCLUSION: These data provide further evidence that variables derived from preoperative CPET can be used to assess risk before elective colorectal surgery.

Randomized controlled trial of stroke volume optimization during elective major abdominal surgery in patients stratified by aerobic fitness.

BACKGROUND: The benefits of stroke volume optimization during surgery are unclear, with recent data not replicating the positive effects of earlier studies. METHODS: This was a randomized controlled trial of standard fluid therapy with or without supplementary blinded intraoperative stroke volume optimization in 220 patients having major elective rectal resection or cystectomy with ileal conduit. All patients were treated using a contemporary enhanced recovery pathway. Interventional fluid challenges used Gelofusine (B Braun, Germany), guided by stoke volume variability measured by LiDCOrapid (LiDCO, UK). Participants were stratified by aerobic fitness (characterized by preoperative cardiopulmonary exercise test), surgical specialty, and intended surgical approach (open or laparoscopic). The primary outcome was the prevalence of moderate or severe complications on day 5 after surgery, defined using the postoperative morbidity survey (POMS) criteria. RESULTS: Patients received ∼13 ml kg(-1) h(-1) of i.v. fluids during surgery. The intervention group received an additional mean (sd) 956 (896) ml Gelofusine. There were no statistically significant differences between groups in any primary or secondary end point. A positive POMS on postoperative day 5 was noted in 54 of 111 control subjects (48.6%) and 55 of 109 participants in the intervention group [50.5%; adjusted odds ratio 0.90 (95% confidence interval 0.52-1.57), P=0.717]. Mean (sd) hospital length of stay was 9.6 (6.8) days in the control group and 11.8 (11.5) days in the intervention group (adjusted difference -2.1 (-4.6 to 0.3) days, P=0.091). There was no statistical interaction between stroke volume optimization and aerobic fitness in terms of rate of complications or length of stay. CONCLUSIONS: Algorithm-driven stroke volume optimization is of no benefit when superimposed on a liberal baseline fluid regimen in patients having elective major abdominal surgery, when stratified to minimize differences in fitness and surgical approach between groups. CLINICAL TRIAL REGISTRATION: ISRCTN21597243.

Patients' inability to perform a preoperative cardiopulmonary exercise test or demonstrate an anaerobic threshold is associated with inferior outcomes after major colorectal surgery.

BACKGROUND: Surgical patients with poor functional capacity, determined by oxygen consumption at anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET), experience longer hospital stays and worse short- and medium-term survival. However, previous studies excluded patients who were unable to perform a CPET or who failed to demonstrate an AT. We hypothesized that such patients are at risk of inferior outcomes after elective surgery. METHODS: All patients undergoing major colorectal surgery attempted CPET to assist in the planning of care. Patients were stratified by their test results into Fit (AT ≥ 11.0 ml O2 kg(-1) min(-1)), Unfit (AT < 11.0 ml O2 kg(-1) min(-1)), or Unable to CPET groups (failed to pedal or demonstrate an AT). For each group, we determined hospital stay and mortality. RESULTS: Between March 2009 and April 2010, 269 consecutive patients were screened, and proceeded to bowel resection. Median hospital stay was 8 days (IQR 5.1-13.4) and there were 44 deaths (16%) at 2 yr; 26 (9.7%) patients were categorized as Unable to CPET, 69 (25.7%) Unfit and 174 (64.7%) Fit. There were statistically significant differences between the three groups in hospital stay [median (IQR) 14.0 (10.5-23.8) vs 9.9 (5.5-15) vs 7.1 (4.9-10.8) days, P < 0.01] and mortality at 2 yr [11/26 (42%) vs 14/69 (20%) vs 19/174 (11%), respectively (P < 0.01)] although the differences between Unable and Unfit were not statistically different. CONCLUSIONS: Patients' inability to perform CPET is associated with inferior outcomes after major colorectal surgery. Future studies evaluating CPET in risk assessment for major surgery should report outcomes for this subgroup.

Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery.

BACKGROUND: Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients. METHODS: In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT. RESULTS: GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls. CONCLUSIONS: Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome. TRIAL REGISTRY: UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.

Systematic review: the use of nitrous oxide gas for lower gastrointestinal endoscopy.

BACKGROUND: Nitrous oxide gas (N(2)O) has been proposed as an alternative to intravenous (i.v.) analgesia in patients undergoing lower gastrointestinal endoscopy. AIM: To perform a systematic review of randomized studies where N(2)O was compared against control in patients undergoing either flexible sigmoidoscopy or colonoscopy. METHODS: Electronic databases were searched; reference lists were checked and letters were sent to authors requesting data. Methodological quality was assessed. Data were tabulated on the duration and difficulty of the procedure, quality of sedation and speed of patient recovery. RESULTS: A total of 11 studies were identified containing 623 patients. No differences were seen between groups for duration, difficulty of procedure or complications. Patient-reported pain was similar for N(2)O when undergoing flexible sigmoidoscopy vs. no sedation and when undergoing colonoscopy vs. i.v. sedation. Differences in delivery of N(2)O were identified. In all studies, N(2)O was associated with a more rapid recovery than i.v. sedation. CONCLUSION: For patients undergoing colonoscopy, N(2)O provides comparable analgesia to i.v. sedation. The rapid psychomotor recovery with N(2)O enables quicker patient discharge and removes the need for a patient to be chaperoned. Benefit was not seen from N(2)O in patients undergoing flexible sigmoidoscopy possibly because it was delivered on demand rather than continuously.

A comparison of patient-controlled analgesia administered by the intravenous or intranasal route during the early postoperative period.

Intranasal administration of lipophilic opioids has been shown to be an effective method of administration which is devoid of major side-effects. Whether it is as effective as intravenous administration for patient-controlled analgesia (PCA) has been investigated for fentanyl and pethidine, but not for diamorphine. This study reports a randomised controlled trial designed to compare the effectiveness of diamorphine administered as PCA utilising either the intranasal or intravenous routes. We investigated 52 consecutive patients undergoing primary lower limb joint replacement surgery. Patients were randomly allocated to receive PCA diamorphine, administered either intravenously (0.5 mg bolus, 3 min lockout) or intranasally (1.0 mg bolus, 3 min lockout). Pain was assessed using a Visual Analogue Score (VAS) at rest and on movement on five occasions over the first 36 h postoperatively. The results demonstrated that patients in the intranasal PCA group had significantly higher VAS scores than the intravenous group, both at rest (intranasal median 35.5 vs. intravenous median 20; p = 0.030) and on movement (intranasal median 64 vs. intravenous median 50; p = 0.016). However, significantly fewer patients in the intranasal group compared with the intravenous group suffered episodes of vomiting (intranasal 0/24 vs. intravenous 6/24 patients; p = 0.022). We suggest that if a maximal reduction in pain score is considered the goal of PCA management, the intravenous route is preferable to the intranasal route.