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Survivors of acute respiratory distress syndrome (ARDS) are at risk of long-term comorbidities. This systematic review and meta-analysis evaluated health-related quality of life (HRQoL), and physical and psychological impairments in ARDS survivors from 3 months to 5 yr follow-up after ICU discharge.Systematic search of PubMed, AMED, BNI, and CINAHL databases from January 2000 to date. The primary outcome was HRQoL. Secondary outcomes included physical, pulmonary, and cognitive function, mental health, and return to work. A secondary analysis compared classical ARDS with severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) ARDS.Forty-eight papers met inclusion criteria including 11 693 patients; of those 85% (n=9992) had classical ARDS and 14% (n=1632) had SARS-CoV-2 ARDS. The 36-Item Short Form Health Survey (SF-36) physical component summary score mean (95% confidence interval [CI]) was 46 (41-50) at 3 months, 39 (36-41) at 6 months, and 40 (38-43) at 12 months. The SF-36 mental component summary mean score was 53 (48-57) at 3 months, 45 (40-50) at 6 months, and 44 (42-47) at 12 months. SF-36 values were lower than those found in the normal population up to 5 yr. The predictive distance walked in 6 min was 57% (45-69), 63% (56-69), and 66% (62-70) at 3, 6, and 12 months, respectively. Classical ARDS and SARS-CoV-2 ARDS showed no difference in HRQoL and physical function; however, patients with classical ARDS had higher incidence of anxiety and depression (P0.001).ARDS survivors can experience reduced HRQoL and physical and mental health impairment. These symptoms might not recover completely up to 5 yr after ICU discharge.PROSPERO: CRD42021296506.

Background Perioperative arterial blood pressure management is a physiologically complex challenge influenced by multiple factors. Methods A multidisciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial pressure as applied to perioperative medicine. We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by National Institute for Health and Care Excellence (NICE) guidelines. Results Multiple physiological factors contribute to the perioperative physiological importance of arterial pressure: (i) arterial pressure is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure because of autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from arterial pressure (haemodynamic incoherence). From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline arterial pressure; (ii) automated and invasive arterial pressure measurements have inherent physiological and technical limitations; (iii) individualised arterial pressure targets may change over time, especially in the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and micro-circulatory control, regional perfusion pressure measurement, and the development of sensitive, specific, and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. Conclusion The multivariable, complex physiology contributing to dynamic changes in perioperative arterial pressure may be underappreciated clinically. The frequently unrecognised dissociation between arterial pressure, organ blood flow, and microvascular and cellular function requires further research to develop a more refined, contextualised clinical approach to this routine perioperative measurement.

Background A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. Methods A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. Results Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. Conclusions Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

The relationship between the dose (volume of fluid) and the effect (increase of stroke volume [SV]) has been poorly described. We hypothesised that the analysis of the dynamic response of SV during fluid challenge (FC) helps to determine the optimal volume of FC, along with its diagnostic accuracy parameters for fluid responsiveness.A prospective observational study was conducted in critically ill patients with circulatory failure. Patients monitored with oesophageal Doppler and assigned to an FC of 500 ml of crystalloid were included. The areas under the curve (AUC) and 95% confidence intervals (CIForty-five patients were included. The AUC increased with cumulative volumes of FC up to 250 ml (AUCA volume of FC of 250 ml with a threshold of 9.6% increase in SV showed the highest accuracy in detecting fluid responsiveness in critically ill patients with shock..

Background Myocardial dysfunction may contribute to circulatory failure in sepsis. There is growing evidence of an association between left ventricular diastolic dysfunction (LVDD) and mortality in septic patients. Utilizing echocardiography, we know that tissue Doppler imaging (TDI) variables e′ and E/e′ are reliable predictors of LVDD and are useful measurements to estimate left ventricular (LV) filling pressures. Methods We conducted a systematic review and meta-analysis to investigate the association of e′ and E/e′ with mortality of patients with severe sepsis or septic shock. In the primary analysis, we included studies providing transthoracic TDI data for e′ and E/e′ and their association with mortality. Subgroup analyses were conducted according to myocardial regional focus of TDI assessment (septal, lateral or averaged). Three secondary analyses were performed: one included data from a transoesophageal study, another excluded studies reporting data at a very early ( 48 h) stage following diagnosis, and the third pooled data only from studies excluding patients with heart valve disease. Results The primary analysis included 16 studies with 1507 patients with severe sepsis and/or septic shock. A significant association was found between mortality and both lower e′ [standard mean difference (SMD) 0.33; 95% confidence interval (CI): 0.05, 0.62; P=0.02] and higher E/e′ (SMD –0.33; 95% CI: –0.57, –0.10; P=0.006). In the subgroup analyses, only the lateral TDI values showed significant association with mortality (lower e′ SMD 0.45; 95% CI: 0.11, 0.78; P=0.009; higher E/e′ SMD –0.49; 95% CI: –0.76, –0.22; P=0.0003). The findings of the primary analysis were confirmed by all secondary analyses. Conclusions There is a strong association between both lower e′ and higher E/e′ and mortality in septic patients.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques. RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P

Summary. The determination of blood flow, i.e. cardiac output, is an integral part of haemodynamic monitoring. This is a review on noninvasive continuous cardiac output monitoring in perioperative and intensive care medicine. We present the underlying principles and validation data of the following technologies: thoracic electrical bioimpedance, thoracic bioreactance, vascular unloading technique, pulse wave transit time, and radial artery applanation tonometry. According to clinical studies, these technologies are capable of providing cardiac output readings noninvasively and continuously. They, therefore, might prove to be innovative tools for the assessment of advanced haemodynamic variables at the bedside. However, for most technologies there are conflicting data regarding the measurement performance in comparison with reference methods for cardiac output assessment. In addition, each of the reviewed technology has its own limitations regarding applicability in the clinical setting. In validation studies comparing cardiac output measurements using these noninvasive technologies in comparison with a criterion standard method, it is crucial to correctly apply statistical methods for the assessment of a technology's accuracy, precision, and trending capability. Uniform definitions for ‘clinically acceptable agreement' between innovative noninvasive cardiac output monitoring systems and criterion standard methods are currently missing. Further research must aim to further develop the different technologies for noninvasive continuous cardiac output determination with regard to signal recording, signal processing, and clinical applicability.

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 ˙ co 2 ) ratio ≥34, heart rate recovery ≤6 and peak oxygen uptake ( V ˙ o 2 ) ≤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 ˙ co 2 ratio ≥34, 200/1250 (16%) had heart rate recovery ≤6, and 396/1250 (32%) had peak V ˙ o 2 ≤14 ml kg −1 min −1 . HR > 87 was independently associated with peak V ˙ o 2 ≤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 ˙ co 2 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.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn .Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis.After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment.Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.

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 (BRS6 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.

Perhaps once every generation, a miracle cure emerges. The effect size is so dramatic as to obviate the need for clinical trials as the difference between the treated and untreated patient is apparent even to the casual observer. Antibiotics were called wonder drugs when they were first introduced because their efficacy was obvious even at the single patient level. However, a century before penicillin, a medical therapy was introduced whose effect on patients was even more dramatic and much more rapid. This therapy was said to ‘reanimate the dead’ and to this day, it is so inextricably linked to the practice of critical care, anaesthesiology, and perioperative medicine that few would have the courage to challenge it. The treatment to which we refer is of course i.v. fluid therapy. The first use of saline for i.v. fluid resuscitation is usually attributed to William O’Shaughnessy, a (then) recent graduate of Edinburgh University Medical School. In 1831, London was in the midst of a cholera epidemic that would eventually claim some 23 000 lives. Having been unimpressed with the effectiveness of the standard treatment of the time (consisting primarily of blood letting), O’Shaughnessy performed a chemical analysis of the blood of patients and concluded that a deficiency of water and ‘normal salts’ was the proximal cause of death. He recommended a dilute salt solution and administered it to dogs without any apparent harm. Reading his account in the Lancet, Dr Thomas Latta of Leith acknowledged and applied O’Shaughnessy’s treatment to patients, with remarkable success. However, the composition of fluid used was decidedly more complex than simple saline, having been made to approximate normal blood plasma, though diluted to replace lost water. Indeed, the solution, if anything, approximated 0.45% saline with some sodium bicarbonate. Nevertheless, medicine’s love affair with salt water can be traced to these early successes in resuscitated cholera victims.

Background Standard treatment practice for the hypotensive patient with poor tissue perfusion is rapid volume resuscitation; in some scenarios, such as septic shock, this is performed with targeted goal-directed endpoints within 6 h of presentation. As a result, patients often develop significant positive fluid accumulation, which has been associated with poor outcomes above certain thresholds. Methods The aim of the current paper is to provide guidance for active pharmacological fluid management in the patient with, or at risk for, clinically significant positive fluid balance from either resuscitation for hypovolaemic shock or acute decompensated heart failure. Results We develop rationale for pharmacological fluid management targets (prevention of worsening fluid accumulation, achievement of slow vs rapid net negative fluid balance) in the context of phases of critical illness provided in the earlier Acute Dialysis Quality Initiative 12 papers.

Background Perioperative mortality after cardiac surgery has decreased in recent years although postoperative morbidity is still significant. Although there is evidence that perioperative goal-directed haemodynamic therapy (GDT) may reduce surgical mortality and morbidity in non-cardiac surgical patients, the data are less clear after cardiac surgery. The objective of this review is to perform a meta-analysis on the effects of perioperative GDT on mortality, morbidity, and length of hospital stay in cardiac surgical patients. Methods We conducted a systematic review using Medline, EMBASE, and the Cochrane Controlled Clinical Trials Register. Additional sources were sought from experts. The inclusion criteria were randomized controlled trials, mortality reported as an outcome, pre-emptive haemodynamic intervention, and cardiac surgical population. Included studies were examined in full and subjected to quantifiable analysis, subgroup analysis, and sensitivity analysis where possible. Data synthesis was obtained by using odds ratio (OR) and mean difference (MD) for continuous data with 95% confidence interval (CI) utilizing a random-effects model. Results From 4986 potential studies, 5 met all the inclusion criteria (699 patients). The quantitative analysis showed that the use of GDT reduced the postoperative complication rate (OR 0.33, 95% CI 0.15–0.73; P =0,006) and hospital length of stay (MD −2.44, 95% CI −4.03 to −0.84; P =0,003). There was no significant reduction in mortality. Conclusion The use of pre-emptive GDT in cardiac surgery reduces morbidity and hospital length of stay.

Background Recent work suggests that increased plasma concentrations of cardiac troponin I (cTnI) are common in critically ill patients and are associated with poor outcome. We measured the frequency of increased plasma cTnI concentrations during patients' stay in a mixed medical/surgical intensive care unit (ICU) and compared our findings with hospital mortality. Methods Basic details, organ support, and hospital mortality were recorded for all patients treated in ICU during a 6 month period. cTnI concentrations were sampled daily for all patients, using 0.04 µg litre−1 as the upper limit of normal, and 0.12 µg litre−1 as an additional stratification point. Results Of 663 patients, 54% were male, with a mean ( sd ) age of 60 (18) yr, 65% were surgical patients, and the median Acute Physiology and Chronic Ill Health II (APACHE II) score was 15 (inter-quartile range 12–20). Increased cTnI concentrations were found in 345 patients (52%) while in ICU. One hundred and twenty patients (18%) died in hospital. cTnI concentration >0.04 µg litre−1 was associated with reduced odds of hospital survival, independent of age, medical admission, unplanned admission, APACHE II score, mechanical ventilation, and haemofiltration (adjusted odds ratio 0.25, 95% confidence interval 0.08–0.75, P=0.014). Stratification by the degree of cTnI increase revealed an incremental trend towards a lower odds of hospital survival, including for patients with ‘minor' elevations of cTnI (0.05–0.12 µg litre−1). Conclusions Increased serum cTnI concentrations during ICU stay independently predicts hospital mortality, even when the threshold is low. We found a trend towards an association between ‘minor' elevations in cTnI and higher in-hospital mortality.