Background:How best to characterize intraoperative hypotension remains unclear. Thus, the authors assessed the relationship between myocardial and kidney injury and intraoperative absolute (mean arterial pressure [MAP]) and relative (reduction from preoperative pressure) MAP thresholds.Methods:The a

Relationship Between Intraoperative Hypotension, Defined by Either Reduction From Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury After Noncardiac Surgery: A Retrospective Cohort Analysis

Subarachnoid hemorrhage (SAH) has deleterious outcomes for patients, and during the hospital stay, patients are susceptible to vasospasm and delayed cerebral ischemia. Coronavirus disease 2019 (COVID-19) has been shown to worsen hypertension through angiotensin-converting enzyme 2 (ACE2) activity, therefore, predisposing to aneurysm rupture. The classic renin-angiotensin pathway activation also predisposes to vasospasm and subsequent delayed cerebral ischemia. Matrix metalloproteinase 9 upregulation can lead to an inflammatory surge, which worsens outcomes for patients. SAH patients with COVID-19 are more susceptible to ventilator-associated pneumonia, reversible cerebral vasoconstriction syndrome, and respiratory distress. Emerging treatments are warranted to target key components of the anti-inflammatory cascade. The aim of this review is to explore how the COVID-19 virus and the intensive care unit (ICU) treatment of severe COVID can contribute to SAH.

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Subarachnoid hemorrhage: management considerations for COVID-19

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.

The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery

Abstract Coronavirus disease 2019 (COVID-19) changed healthcare across the world. With this change came an increase in healthcare-associated infections (HAIs) and a concerning concurrent proliferation of MDR organisms (MDROs). In this narrative review, we describe the impact of COVID-19 on HAIs and MDROs, describe potential causes of these changes, and discuss future directions to combat the observed rise in rates of HAIs and MDRO infections.

https://academic.oup.com/jacamr/article-pdf/5/1/dlac130/48476829/dlac130.pdf

The impact of COVID-19 on multidrug-resistant organisms causing healthcare-associated infections: a narrative review

Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting.We conducted a systematic peer review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, their definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values; and they were classified according to the type of surgery (cardiac and non-cardiac).A total of 3,680 articles were identified, and 66 articles fulfilled the criteria for data extraction. For the perioperative setting, the number of articles varies by outcome: 20 mortality, 16 renal outcomes, 6 stroke, 7 delirium and 34 other outcomes. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from the patient's baseline blood pressure (BP) (OR 1.02-1.36); hypotension also had a role in the development of acute kidney injury (AKI) (OR 1.03-14.11). Postsurgical delirium was found in relation with BP lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). Increased OR (37.67) of intracranial hemorrhage was associated to postsurgical systolic BP >130 mmHg. There was a wide range of additional diverse outcomes related to hypo-, hypertension and BP lability.The perioperative management of BP influences short- and long-term effects of surgical procedures in cardiac and non-cardiac interventions; these findings support the burden of BP fluctuations in this setting. 

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The burden of perioperative hypertension/hypotension: A systematic review

Hip fracture is a growing healthcare challenge, with 6–8% 30-day mortality and 20–30% of patients incurring major morbidity, including impaired mobilisation and ability to live independently. While observational studies have shown no benefit of general versus spinal anaesthesia on 30-day mortality, intraoperative hypotension during hip fracture surgery is associated with increased 30-day mortality regardless of anaesthetic technique. Although a recent trial on younger patients demonstrated reduced postoperative complications by maintaining intraoperative arterial blood pressure close to preoperative baseline, there are no data correlating intraoperative hypotension during hip fracture surgery with postoperative morbidity. We evaluated the hypothesis that duration and severity of intraoperative hypotension during hip fracture surgery is associated with increased postoperative morbidity. A retrospective analysis was carried out on n = 52 patients undergoing hip fracture surgery between January and June 2017. Measurements of patients’ intraoperative systolic arterial pressure (SAP) and mean arterial pressure (MAP) during anaesthesia, logged electronically through an anaesthesia information management system, were reviewed. We calculated the total duration of time where SAP or MAP were below pre-defined thresholds for hypotension (MAP < 75 mmHg, MAP < 55 mmHg, SAP ≤ 80% admission baseline or SAP ≤ 80% pre-induction baseline). Univariate and bivariate descriptive statistics were generated for all relevant variables. With multivariable regression models containing known predictors, cumulative duration of hypotension was correlated with postoperative comorbidities as quantified by the Clavien-Dindo and Comprehensive Complication Indices. Mean age (± SD) was 78 ± 13 years, 75% were female, 87% were ASA II or III and 60% underwent spinal anaesthesia. Mean Comprehensive Complication Index was 20.4 ± 19.2. Lowest absolute SAP and MAP values were 82 ± 18 mmHg and 55 ± 12 mmHg respectively. Cumulative time of SAP < 80% pre-induction value adjusted to gender, age and the Charlson Comorbidity Index was associated with progression to a higher Clavien-Dindo classification (odds ratio 1.020 per additional minute; 95% CI 1.008–1.035; P = 0.003). In this exploratory retrospective analysis, the cumulative time of hypotension during hip fracture surgery correlated with extensive postoperative morbidity when adjusting to other known predictors. Intraoperative cumulative time of hypotension may be a good candidate for larger prediction studies as a predictor of postoperative complications. A randomised controlled trial evaluating the effect of actively minimising intraoperative hypotension on postoperative morbidity in hip fracture patients seems warranted.

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Hypotension during hip fracture surgery and postoperative morbidity

ABSTRACT Introduction Ventilator-associated pneumonia (VAP) is common; its prevalence has been highlighted by the Covid-19 pandemic. Even young patients can suffer severe nosocomial infection and prolonged mechanical ventilation. Multidrug-resistant bacteria can spread alarmingly fast around the globe and new antimicrobials are struggling to keep pace; hence physicians must stay abreast of new developments in the treatment of nosocomial pneumonia and VAP. Areas Covered This narrative review examines novel antimicrobial investigational drugs and their implementation in the ICU setting for VAP. This paper highlights novel approaches such as monoclonal antibody treatments for P. aeruginosa and S. aureus and phage antibiotic synthesis. This paper also examines mechanisms of resistance in Gram-negative bacteria, virulence factors, and inhaled antibiotics and questions what may be on the horizon in terms of emerging treatment strategies. Expert opinion The postantibiotic era is rapidly approaching, and the need for personalized medicine, point-of-care microbial sensitivity testing, and development of biomarkers for severe infections is clear. Results from emerging and new antibiotics are encouraging, but infection control measures and de-escalation protocols must be employed to prolong their usefulness in critical illness.

Novel investigational treatments for ventilator-associated pneumonia and critically ill patients in the intensive care unit

Sepsis is one of the most common and deadly syndromes faced in Intensive Care settings globally. Recent advances in bedside imaging have defined the changes in the microcirculation in sepsis. One of the most advocated interventions for sepsis is fluid therapy. Whether or not fluid bolus affects the microcirculation in sepsis has not been fully addressed in the literature. This systematic review of the evidence aims to collate studies examining the microcirculatory outcomes after a fluid bolus in patients with sepsis. We will assimilate the evidence for using handheld intra vital microscopes to guide fluid resuscitation and the effect of fluid bolus on the sublingual microcirculation in patients with sepsis and septic shock. We conducted a systematic search of Embase, CENTRAL and Medline (PubMed) using combinations of the terms “microcirculation” AND “fluid” OR “fluid resuscitation” OR “fluid bolus” AND “sepsis” OR “septic shock”. We found 3376 potentially relevant studies. Fifteen studies published between 2007 and 2021 fulfilled eligibility criteria to be included in analysis. The total number of participants was 813; we included six randomized controlled trials and nine non-randomized, prospective observational studies. Ninety percent used Sidestream Dark Field microscopy to examine the microcirculation and 50% used Hydroxyethyl Starch as their resuscitation fluid. There were no clear effects of fluid on the microcirculation parameters. There was too much heterogeneity between studies and methodology to perform meta-analysis. Studies identified heterogeneity of affect in the sepsis population, which could mean that current clinical classifications were not able to identify different microcirculation characteristics. Use of microcirculation as a clinical endpoint in sepsis could help to define sepsis phenotypes. More research into the effects of different resuscitation fluids on the microcirculation is needed.

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Effects of Fluids on the Sublingual Microcirculation in Sepsis

Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.

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Endothelial Damage and the Microcirculation in Critical Illness

Background The severe form of COVID-19 can cause a dysregulated host immune syndrome that might lead patients to death. To understand the underlying immune mechanisms that contribute to COVID-19 disease we have examined 28 different biomarkers in two cohorts of COVID-19 patients, aiming to systematically capture, quantify, and algorithmize how immune signals might be associated to the clinical outcome of COVID-19 patients. Methods The longitudinal concentration of 28 biomarkers of 95 COVID-19 patients was measured. We performed a dimensionality reduction analysis to determine meaningful biomarkers for explaining the data variability. The biomarkers were used as input of artificial neural network, random forest, classification and regression trees, k-nearest neighbors and support vector machines. Two different clinical cohorts were used to grant validity to the findings. Results We benchmarked the classification capacity of two COVID-19 clinicals studies with different models and found that artificial neural networks was the best classifier. From it, we could employ different sets of biomarkers to predict the clinical outcome of COVID-19 patients. First, all the biomarkers available yielded a satisfactory classification. Next, we assessed the prediction capacity of each protein separated. With a reduced set of biomarkers, our model presented 94% accuracy, 96.6% precision, 91.6% recall, and 95% of specificity upon the testing data. We used the same model to predict 83% and 87% (recovered and deceased) of unseen data, granting validity to the results obtained. Conclusions In this work, using state-of-the-art computational techniques, we systematically identified an optimal set of biomarkers that are related to a prediction capacity of COVID-19 patients. The screening of such biomarkers might assist in understanding the underlying immune response towards inflammatory diseases.

An artificial neural network classification method employing longitudinally monitored immune biomarkers to predict the clinical outcome of critically ill COVID-19 patients

Rachael Cusack

Papers

Hypotension during hip fracture surgery and postoperative morbidity

Novel investigational treatments for ventilator-associated pneumonia and critically ill patients in the intensive care unit

Effects of Fluids on the Sublingual Microcirculation in Sepsis

Endothelial Damage and the Microcirculation in Critical Illness

An artificial neural network classification method employing longitudinally monitored immune biomarkers to predict the clinical outcome of critically ill COVID-19 patients