ORCID Profile
0000-0002-3859-679X
Current Organisations
Duke University
,
University College Hospital
,
University College London
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Publisher: Elsevier BV
Date: 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1093/BJA/AEW257
Abstract: Baroreflex dysfunction is a common feature of established cardiometabolic diseases that are most frequently associated with the development of critical illness. Laboratory models show that baroreflex dysfunction impairs cardiac contractility and cardiovascular performance, thereby increasing the risk of morbidity after trauma and sepsis. We hypothesized that baroreflex dysfunction contributes to excess postoperative morbidity after major surgery as a consequence of the inability to achieve adequate perioperative tissue oxygen delivery. In a randomized controlled trial of goal-directed haemodynamic therapy (GDT) in higher-risk surgical patients, baroreflex function was assessed using the spontaneous baroreflex sensitivity (BRS) method via an arterial line placed before surgery, using a validated sequence method technique (one beat lag). The BRS was calculated during the 6 h postoperative GDT intervention. Analyses of BRS were done by investigators blinded to clinical outcomes. The primary outcome was the association between postoperative baroreflex dysfunction (BRS <6 mm Hg s(-1), a negative prognostic threshold in cardiovascular pathology) and early postoperative morbidity. The relationship between baroreflex dysfunction and postoperative attainment of preoperative indexed oxygen delivery was also assessed. Patients with postoperative baroreflex dysfunction were more likely to sustain infectious {relative risk (RR) 1.75 [95% confidence interval (CI): 1.07-2.85], P=0.02} and cardiovascular morbidity [RR 2.39 (95% CI: 1.22-4.71), P=0.008]. Prolonged hospital stay was more likely in patients with baroreflex dysfunction [unadjusted hazard ratio 1.62 (95% CI: 1.14-2.32), log-rank P=0.004]. Postoperative O2 delivery was 36% (95% CI: 7-65) lower in patients with baroreflex dysfunction in those not randomly assigned to GDT (P=0.02). Baroreflex dysfunction is associated with excess morbidity, impaired cardiovascular performance, and delayed hospital discharge, suggesting a mechanistic role for autonomic dysfunction in determining perioperative outcome. ISCRTN76894700.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BJA.2017.11.009
Abstract: 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. 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). 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]. 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. ISRCT registry, ISRCTN88456378.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1093/BJA/AEX164
Abstract: Elevated preoperative heart rate (HR) is associated with perioperative myocardial injury and death. In apparently healthy in iduals, 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). 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. 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 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). Elevated preoperative heart rate is associated with impaired cardiopulmonary performance consistent with clinically unsuspected, subclinical cardiac failure. ISRCTN88456378.
Publisher: Public Library of Science (PLoS)
Date: 21-08-2019
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Whittle.