Background: Intraoperative hypotension (IOH) during non-cardiac surgery is common and associated with major adverse kidney, neurological and cardiac events and even death. Given that IOH is a modifiable risk factor for the mitigation of postoperative complications, it is imperative to generate a precise definition for IOH to facilitate strategies for avoiding or treating its occurrence. Moreover, a universal and consensus definition of IOH may also facilitate the application of novel and emerging therapeutic interventions in treating IOH. We conducted a review to systematically record the reported definitions of intraoperative hypotension in adults undergoing non-cardiac surgery under general anaesthesia. Methods: In accordance with Cochrane guidelines, we searched three online databases (OVID [Medline], Embase and Cochrane Library) for all studies published from 1 January 2000 to 6 September 2020. We evaluated the number of studies that reported the absolute or relative threshold values for defining blood pressure. Secondary aims included evaluation of the threshold values for defining IOH, the methodology for accounting for the severity of hypotension, whether the type of surgical procedure influenced the definition of IOH, and whether a study whose definition of IOH aligned with the Perioperative Quality Initiative-3 workgroup (POQI) consensus statement for defining was more likely to be associated with determining an adverse postoperative outcome. Results: A total of 318 studies were included in the final qualitative synthesis. Most studies (n = 249; 78.3%) used an absolute threshold to define hypotension; 150 (60.5%) reported SBP, 117 (47.2%) reported MAP, and 12 (4.8%) reported diastolic blood pressure (DBP). 126 (39.6%) used a relative threshold to define hypotension. Of the included studies, 153 (48.1%) did not include any duration variable in their definition of hypotension. Among the selected 318 studies 148 (46.5%) studies defined IOH according to the POQI statement. When studies used a “relative blood pressure change” to define IOH, there was a weaker association in detecting adverse postoperative outcomes compared to studies who reported “absolute blood pressure change” (χ²(2) = 10.508, P = 0.005, Cramér’s V = 0.182). When studies used the POQI statement definition of hypotension or defined IOH by values higher than the POQI statement definition there were statistical differences observed between IOH and adverse postoperative outcomes (χ²(1) = 6.581, P = 0.037, Cramér’s V = 0.144). When both the duration of IOH or the numbers of hypotensive epochs were evaluated, we observed a significantly stronger relationship between the definition of IOH use the development of adverse postoperative outcomes. (χ²(1) = 4.860, P = 0.027, Cramér’s V = 0.124). Conclusions: Most studies defined IOH by absolute or relative changes from baseline values. There are substantial inconsistencies in how IOH was reported. Further, definitions differed across different surgical specialities. Our findings further suggest that IOH should be defined using the absolute values stated in the POQI statement i.e., MAP < 60–70 mmHg or SBP < 100 mmHg. Finally, the number of hypotensive epochs or time-weighted duration of IOH should also be reported.

Summary: Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre‐operative non‐anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron‐deficient group of patients undergoing cardiac surgery with an iron‐replete group. Consecutive non‐anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron‐deficient (n = 109) and iron‐replete (n = 168) groups. Compared with the iron‐replete group, patients in the iron‐deficient group were more likely to be female (43% vs. 12%, iron‐replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre‐operative EuroSCORE (median IQR [range]) 3 (2–5 [0–10]) vs. 3 (2–4 [0–9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l ⁻¹ . Univariate analysis suggested that iron‐deficient patients had a longer hospital length of stay (7 (6–9 [2–40]) vs. 7 (5–8 [4–23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80–84 [0–87]) vs. 83 (81–85 [34–86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre‐operative age, sex, renal function, Euro SCORE and haemoglobin, the mean increase in hospital length of stay in the iron‐deficient group relative to the iron‐replete group was 0.86 days (bootstrapped 95%CI −0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non‐anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.

Background: The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio.Methods and findings: We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.govIdentifier: NCT03532594).Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes;p= 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78–1.14] vs. 0.75 [IQR 0.57–0.99];p< 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75–245] vs. 135 [IQR 94–222] mL;p= 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%]p= 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160–210] vs. 280 [IQR 250–300] mg;p< 0.001).Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C).Conclusions: Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients.Trial registration: ClinicalTrials.gov Unique identifierNCT03532594.

Summary: Introduction: Central venous pressure has been a key component of haemodynamic monitoring for several decades, but its clinical utility is still debated. While central venous pressure has been used traditionally to assess intravascular volume status and fluid responsiveness, mounting evidence suggests that its absolute value alone is an unreliable predictor of such states. This narrative review explores the historical development and physiological foundations of central venous pressure, its measurement techniques and the available evidence regarding central venous pressure monitoring in various clinical scenarios. Methods: We conducted a literature search to identify relevant articles. The abstracts of identified articles were assessed for relevance, and their references were screened for further relevant publications. Results: We identified 229 articles, with 72 undergoing full text extraction and data synthesis. Preliminary work in central venous pressure monitoring began in canines, before early human studies and the development of Guytonian principles of haemodynamics. Physiologically, central venous pressure reflects intraluminal pressure of the superior vena cava, with measurement affected significantly by transducer position, catheter position and intrathoracic pressures. In right ventricular dysfunction, the central venous pressure waveform loses its x‐descent, as the y‐descent becomes exaggerated. Central venous pressure in isolation is considered a poor predictor of volume responsiveness; however, elevated central venous pressure is linked with impaired tissue perfusion and poor clinical outcomes, including acute kidney injury and higher risk of mortality in certain patient cohorts. Discussion: Although reliance on central venous pressure as a singular guide for fluid resuscitation is discouraged, it remains a valuable tool when interpreted in conjunction with waveform analysis and trend monitoring, offering insights into right heart function, venous congestion and organ perfusion. As patient cohorts grow increasingly complex, a nuanced understanding of central venous pressure waveforms and trends is essential for optimising management strategies in peri‐operative and critical care settings.