Our results suggest that the PLR-TEB is a feasible method in spontaneously breathing volunteers with reasonable reproducibility. The age and baseline stroke volume effect suggests a more complex underlying physiology than commonly appreciated. The fact that half of the volunteers had a positive preload response, against the 10% threshold, leads to questions about how this measurement should be used in emergency care and will help shape future patient studies.

Background: Myocardial injury is more frequent after noncardiac surgery in patients with preoperative cardiac vagal dysfunction, as quantified by delayed heart rate (HR) recovery after cessation of cardiopulmonary exercise testing. We hypothesised that serial and dynamic measures of cardiac vagal activity are also associated with myocardial injury after noncardiac surgery. Methods: Serial autonomic measurements were made before and after surgery in patients undergoing elective noncardiac surgery. Cardiac vagal activity was quantified by HR variability and HR recovery after orthostatic challenge (supine to sitting). Revised cardiac risk index (RCRI) was calculated for each patient. The primary outcome was myocardial injury (high-sensitivity troponin !15 ng L À1 ) within 48 h of surgery, masked to investigators. The exposure of interest was cardiac vagal activity (high-frequency power spectral analysis [HF Ln ]) and HR recovery 90 s from peak HR after the orthostatic challenge. Results: Myocardial injury occurred in 48/189 (25%) patients, in whom 41/48 (85%) RCRI was <2. In patients with myocardial injury, vagal activity (HF Ln ) declined from 5.15 (95% confidence interval [CI]: 4.58e5.72) before surgery to 4.33 (95% CI: 3.76e4.90; P<0.001) 24 h after surgery. In patients who remained free of myocardial injury, HF Ln did not change (4.95 [95% CI: 4.64e5.26] before surgery vs 4.76 [95% CI: 4.44e5.08] after surgery). Before and after surgery, the orthostatic HR recovery was slower in patients with myocardial injury (5 beats min À1 [95% CI: 3e7]), compared with HR recovery in patients who remained free of myocardial injury (10 beats min À1 [95% CI: 7e12]; P¼0.02). Conclusions: Serial HR measures indicating loss of cardiac vagal activity are associated with perioperative myocardial injury in lower-risk patients undergoing noncardiac surgery.

Background: Pain is a common complaint in patients attending the emergency department and historically it is under-assessed and undertreated. Previous research is heterogeneous and does not well describe pain in emergency departments (EDs) over time. Our aim was to describe pain in a UK emergency department by using a sample that included every adult attendance over the course of one week.

Background Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery. Methods In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min -1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals). Results 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14–1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05–1.62);p = 0.02)), infective (OR:1.38 (1.10–1.72); p = 0.006), renal (OR:1.91 (1.30–2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15–1.69); p<0.001)), neurological (OR:1.73 (1.11–2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14–1.68); p = 0.001) within 5 days of surgery. Conclusions Multi-organ dysfunction is more common in surgical patients with cardiac vagal dysfunction, defined as HRR ≤ 12 bpm after preoperative cardiopulmonary exercise testing. Clinical trial registry ISRCTN88456378 .