Outlying End-Tidal Carbon Dioxide During General Anesthesia Is Associated With Postoperative Pulmonary Complications: A Multicenter Retrospective Observational Study From US Hospitals Between 2010 and 2017.

BACKGROUND: Postoperative pulmonary complications (PPCs) occur in up to 33% of patients who undergo noncardiothoracic surgery. Emerging evidence suggests that permissive hypercapnia may reduce the risk of lung injury. We hypothesized that higher intraoperative end-tidal carbon dioxide (Etco2) concentrations would be associated with a decreased risk of PPCs. METHODS: This retrospective, observational, multicenter study included patients undergoing general anesthesia for noncardiothoracic procedures (January 2010-December 2017). The primary outcome was PPC within 30 postoperative days. Secondary outcomes were PPC within 1 week, postoperative length of stay, and inhospital 30-day mortality. The association between these outcomes, median Etco2, and 4 time-weighted average area-under-the-curve (TWA-AUC) thresholds (<28, <35, <45, and >45 mm Hg) was explored using a multivariable mixed-effect model and by plotting associated risks. RESULTS: Among 143,769 cases across 11 hospitals, 10,276 (7.1%) experienced a PPC. When compared to a baseline median Etco2 of 35 to 40 mm Hg, a median Etco2 >40 mm Hg was associated with an increase in PPCs within 30 days (median Etco2, 40-45 mm Hg; adjusted OR, 1.16 [99% confidence interval {CI}, 1.00-1.33]; P value = .008 and median Etco2, >45 mm Hg; OR, 1.64 [99% CI, 1.33-2.02]; P value < .001). The occurrence of any Etco2 value <28 mm Hg (ie, a positive TWA-AUC < 28 mm Hg) was associated with PPCs (OR, 1.40 [95% CI, 1.33-1.49]; P value < .001), mortality, and length of stay. Any Etco2 value >45 mm Hg (ie, a positive TWA-AUC >45 mm Hg) was also associated with PPCs (OR, 1.24 [95% CI, 1.17-1.31]; P < .001). The Etco2 range with the lowest incidence of PPCs was 35 to 38 mm Hg. CONCLUSIONS: Both a very low (<28 mm Hg) and a high Etco2 (>45 mm Hg) were associated with PPCs within 30 days. The lowest PPC incidence was found in patients with an Etco2 of 35 to 38 mm Hg. Prospective studies are needed to clarify the relationship between postoperative PPCs and intraoperative Etco2.

Intraoperative hypotension and delirium among older adults undergoing transcatheter aortic valve replacement.

BACKGROUND: Postoperative delirium (POD) is a frequently observed complication after transcatheter aortic valve replacement (TAVR). The effects of intraoperative hypotension (IOH) on POD occurrence are currently unclear. METHODS: A retrospective observational cohort study of patients who underwent TAVR was conducted. We predefined IOH as area under the threshold (AUT) of five mean arterial blood pressures (MBP), varying from <100 to <60 mmHg. The AUT consisted of the combination of duration and depth under the MBP thresholds, expressed in mmHg*min. All MBP AUTs were computed based on the complete procedure, independent of procedural phase or duration. RESULTS: This cohort included 675 patients who underwent TAVR under general anesthesia (n = 128, 19%) or procedural sedation (n = 547, 81%). Delirium occurred mostly during the first 2 days after TAVR, and was observed in n = 93 (14%) cases. Furthermore, 674, 672, 663, 630, and 518 patients had at least 1 min intraoperative MBP <100, <90, <80, <70, and <60 mmHg, respectively. Patients who developed POD had higher AUT based on all five MBP thresholds during TAVR. The penalized adjusted odds ratio varied between 1.08 (99% confidence interval [CI] 0.74-1.56) for the AUT based on MBP < 100 mmHg and OR 1.06 (99% CI 0.88-1.28) for the AUT based on MBP < 60 mmHg. CONCLUSIONS: Intraoperative hypotension is frequently observed during TAVR, but not independently associated with POD after TAVR. Other potential factors than intraoperative hypotension may explain the occurrence of delirium after TAVR.

Preoperative MRI brain phenotypes are related to postoperative delirium in older individuals.

The underlying structural correlates of predisposition to postoperative delirium remain largely unknown. A combined analysis of preoperative brain magnetic resonance imaging (MRI) markers could improve our understanding of the pathophysiology of delirium. Therefore, we aimed to identify different MRI brain phenotypes in older patients scheduled for major elective surgery, and to assess the relation between these phenotypes and postoperative delirium. Markers of neurodegenerative and neurovascular brain changes were determined from MRI brain scans in older patients (n = 161, mean age 71, standard deviation 5 years), of whom 24 (15%) developed delirium. A hierarchical cluster analysis was performed. We found six distinct groups of patients with different MRI brain phenotypes. Logistic regression analysis showed a higher odds of developing postoperative delirium in individuals with multi-burden pathology (n = 15 (9%), odds ratio (95% confidence interval): 3.8 (1.1-13.0)). In conclusion, these results indicate that different MRI brain phenotypes are related to a different risk of developing delirium after major elective surgery. MRI brain phenotypes could assist in an improved understanding of the structural correlates of predisposition to postoperative delirium.

Artifacts annotations in anesthesia blood pressure data by man and machine.

Physiologic data from anesthesia monitors are automatically captured. Yet erroneous data are stored in the process as well. While this is not interfering with clinical care, research can be affected. Researchers should find ways to remove artifacts. The aim of the present study was to compare different artifact annotation strategies, and to assess if a machine learning algorithm is able to accept or reject individual data points. Non-cardiac procedures requiring invasive blood pressure monitoring were eligible. Two trained research assistants observed procedures live for artifacts. The same procedures were also retrospectively annotated for artifacts by a different person. We compared the different ways of artifact identifications and modelled artifacts with three different learning algorithms (lasso restrictive logistic regression, neural network and support vector machine). In 88 surgical procedures including 5711 blood pressure data points, the live observed incidence of artifacts was 2.1% and the retrospective incidence was 2.2%. Comparing retrospective with live annotation revealed a sensitivity of 0.32 and specificity of 0.98. The performance of the learning algorithms which we applied ranged from poor (kappa 0.053) to moderate (kappa 0.651). Manual identification of artifacts yielded different incidences in different situations, which were not comparable. Artifact detection in physiologic data collected during anesthesia could be automated, but the performance of the learning algorithms in the present study remained moderate. Future research should focus on optimization and finding ways to apply them with minimal manual work. The present study underlines the importance of an explicit definition for artifacts in database research.

Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study.

BACKGROUND: Continuous infusions of norepinephrine to treat perioperative hypotension are typically administered through a central venous line rather than a peripheral venous catheter to avoid the risk of localized tissue necrosis in case of drug extravasation. There is limited literature to estimate the risk of skin necrosis when peripheral norepinephrine is used to counteract anesthesia-associated hypotension in elective surgical cases. This study aimed to estimate the rate of occurrence of drug-related adverse effects, including skin necrosis requiring surgical management when norepinephrine peripheral extravasation occurs. METHODS: This retrospective cohort study used the perioperative databases of the University Hospitals in Amsterdam and Utrecht, the Netherlands, to identify surgical patients who received norepinephrine peripheral intravenous infusions (20 µg/mL) between 2012 and 2016. The risk of drug-related adverse effects, including skin necrosis, was estimated. Particular care was taken to identify patients who needed plastic surgical or medical attention secondary to extravasation of dilute, peripheral norepinephrine. RESULTS: A total of 14,385 patients who received norepinephrine peripheral continuous infusions were identified. Drug extravasation was observed in 5 patients (5/14,385 = 0.035%). The 95% confidence interval (CI) for infusion extravasation was 0.011%-0.081%, indicating an estimated risk of 1-8 events per every 10,000 patients. There were zero related complications requiring surgical or medical intervention, resulting in a 95% CI of 0%-0.021% and indicating a risk of approximately 0-2 events per 10,000 patients. CONCLUSIONS: In the current database analysis, no significant association was found between the use of peripheral intravenous norepinephrine infusions and adverse events.

Artifact Processing Methods Influence on Intraoperative Hypotension Quantification and Outcome Effect Estimates.

BACKGROUND: Physiologic data that is automatically collected during anesthesia is widely used for medical record keeping and clinical research. These data contain artifacts, which are not relevant in clinical care, but may influence research results. The aim of this study was to explore the effect of different methods of filtering and processing artifacts in anesthesiology data on study findings in order to demonstrate the importance of proper artifact filtering. METHODS: The authors performed a systematic literature search to identify artifact filtering methods. Subsequently, these methods were applied to the data of anesthesia procedures with invasive blood pressure monitoring. Different hypotension measures were calculated (i.e., presence, duration, maximum deviation below threshold, and area under threshold) across different definitions (i.e., thresholds for mean arterial pressure of 50, 60, 65, 70 mmHg). These were then used to estimate the association with postoperative myocardial injury. RESULTS: After screening 3,585 papers, the authors included 38 papers that reported artifact filtering methods. The authors applied eight of these methods to the data of 2,988 anesthesia procedures. The occurrence of hypotension (defined with a threshold of 50 mmHg) varied from 24% with a median filter of seven measurements to 55% without an artifact filtering method, and between 76 and 90% with a threshold of 65 mmHg. Standardized odds ratios for presence of hypotension ranged from 1.16 (95% CI, 1.07 to 1.26) to 1.24 (1.14 to 1.34) when hypotension was defined with a threshold of 50 mmHg. Similar variations in standardized odds ratios were found when applying methods to other hypotension measures and definitions. CONCLUSIONS: The method of artifact filtering can have substantial effects on estimates of hypotension prevalence. The effect on the association between intraoperative hypotension and postoperative myocardial injury was relatively small. Nevertheless, the authors recommend that researchers carefully consider artifacts handling and report the methodology used.

Patient and anesthesia characteristics of children with low pre-incision blood pressure: A retrospective observational study.

BACKGROUND: Intraoperative blood pressure has been suggested as a key factor for safe pediatric anesthesia. However, there is not much insight into factors that discriminate between children with low and normal pre-incision blood pressure. Our aim was to explore whether children who have a low blood pressure during anesthesia are different than those with normal blood pressure. The focus of the present study was on the pre-incision period. METHODS: This retrospective study included pediatric patients undergoing anesthesia for non-cardiac surgery at a tertiary pediatric university hospital, between 2012 and 2016. We analyzed the association between pre-incision blood pressure and patient- and anesthesia characteristics, comparing low with normal pre-incision blood pressure. This association was further explored with a multivariable linear regression. RESULTS: In total, 20 962 anesthetic cases were included. Pre-incision blood pressure was associated with age (beta -0.04 SD per year), gender (female -0.11), previous surgery (-0.15), preoperative blood pressure (+0.01 per mm Hg), epilepsy (0.12), bronchial hyperactivity (-0.18), emergency surgery (0.10), loco-regional technique (-0.48), artificial airway device (supraglottic airway device instead of tube 0.07), and sevoflurane concentration (0.03 per sevoflurane %). CONCLUSIONS: Children with low pre-incision blood pressure do not differ on clinically relevant factors from children with normal blood pressure. Although the present explorative study shows that pre-incision blood pressure is partly dependent on patient characteristics and partly dependent on anesthetic technique, other unmeasured variables might play a more important role.

Incidence of Artifacts and Deviating Values in Research Data Obtained from an Anesthesia Information Management System in Children.

BACKGROUND: Vital parameter data collected in anesthesia information management systems are often used for clinical research. The validity of this type of research is dependent on the number of artifacts. METHODS: In this prospective observational cohort study, the incidence of artifacts in anesthesia information management system data was investigated in children undergoing anesthesia for noncardiac procedures. Secondary outcomes included the incidence of artifacts among deviating and nondeviating values, among the anesthesia phases, and among different anesthetic techniques. RESULTS: We included 136 anesthetics representing 10,236 min of anesthesia time. The incidence of artifacts was 0.5% for heart rate (95% CI: 0.4 to 0.7%), 1.3% for oxygen saturation (1.1 to 1.5%), 7.5% for end-tidal carbon dioxide (6.9 to 8.0%), 5.0% for noninvasive blood pressure (4.0 to 6.0%), and 7.3% for invasive blood pressure (5.9 to 8.8%). The incidence of artifacts among deviating values was 3.1% for heart rate (2.1 to 4.4%), 10.8% for oxygen saturation (7.6 to 14.8%), 14.1% for end-tidal carbon dioxide (13.0 to 15.2%), 14.4% for noninvasive blood pressure (10.3 to 19.4%), and 38.4% for invasive blood pressure (30.3 to 47.1%). CONCLUSIONS: Not all values in anesthesia information management systems are valid. The incidence of artifacts stored in the present pediatric anesthesia practice was low for heart rate and oxygen saturation, whereas noninvasive and invasive blood pressure and end-tidal carbon dioxide had higher artifact incidences. Deviating values are more often artifacts than values in a normal range, and artifacts are associated with the phase of anesthesia and anesthetic technique. Development of (automatic) data validation systems or solutions to deal with artifacts in data is warranted.

Long-Term Self-Reported Cognitive Problems After Delirium in the Intensive Care Unit and the Effect of Systemic Inflammation.

OBJECTIVES: To describe the association between intensive care unit (ICU) delirium and self-reported cognitive problems in 1-year ICU survivors, and investigate whether this association was altered by exposure to systemic inflammation during ICU stay. DESIGN: Prospective cohort study. SETTING: Dutch medical-surgical ICU. PARTICIPANTS: One-year ICU survivors, admitted to the ICU ≥48 hours. MEASUREMENTS: Self-reported cognitive problems were measured with the Cognitive Failures Questionnaire (CFQ). Cumulative exposure to systemic inflammation was based on all daily C-reactive protein (CRP) measurements during ICU stay, expressed as the area under the curve (AUC). Multivariable linear regression was conducted to evaluate the association between delirium and the CFQ. The effect of inflammation on the association between delirium and CFQ was assessed, comparing the effect estimate (B) of delirium and CFQ between models with and without inclusion of the AUC of CRP. RESULTS: Among 567 1-year ICU survivors, the CFQ was completed by 363 subjects. Subjects with multiple days of delirium during ICU stay reported more self-reported cognitive problems (Badj = 5.10, 95% CI 1.01-9.20), whereas a single day delirium was not associated with higher CFQ scores (Badj = -0.72, 95% CI -5.75 to 4.31). Including the AUC of CRP did not change the association between delirium and the CFQ (ratio for a single and multiple days were respectively: 1.00, 95%CI 0.59-1.44 and 0.86, 95% CI 0.47-1.16). CONCLUSION: Multiple days of delirium was associated with long-term self-reported cognitive problems. The cumulative exposure to systemic inflammation did not alter this association, suggesting that delirium in the context of little inflammation is also detrimental.

Relationship Between Preoperative Evaluation Blood Pressure and Preinduction Blood Pressure: A Cohort Study in Patients Undergoing General Anesthesia.

BACKGROUND: For outcomes research where changes in intraoperative blood pressure are a possible causative factor, it is important to determine an appropriate source for a reference value. We studied to what extent preinduction blood pressure values in the operating room differ from those obtained during preoperative evaluation outside the operating room. METHODS: Cohort study including 4408 patients aged 60 years or older undergoing noncardiac surgery. The outcome was the difference between the preinduction mean blood pressure (MBP) and the MBP obtained during preoperative evaluation. A difference of ≥10 mm Hg was considered clinically relevant. A paired samples t test was used to estimate the difference. Linear regression was used to obtain estimates adjusted for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure. RESULTS: Complete data were available for 3660 (83%) patients. There were 2228 (61%) patients with a difference of ≥10 mm Hg between the preinduction and preoperative MBP. The overall mean difference between both MBPs was 11 mm Hg (95% confidence interval, 10-11) with important variability among individuals. Patients with higher preoperative MBP values had smaller differences. After adjusting for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure, the difference decreased an estimated 5.0 mm Hg (95% confidence interval, 4.7-5.4) for every increase of 10 mm Hg in preoperative MBP. Patient characteristics, comorbidity, type of surgery, or medication were not strongly associated with the difference. CONCLUSIONS: The average preinduction blood pressure was higher than the preoperative blood pressure. This difference between the measurements can be explained by stress-induced effects and regression to the mean. To define an optimal reference value for research purposes or to arrive at a clinical perioperative blood pressure target, one should consider that there is important variability both within and between patients.

Reference Values for Noninvasive Blood Pressure in Children during Anesthesia: A Multicentered Retrospective Observational Cohort Study.

BACKGROUND: Although noninvasive blood pressure (NIBP) monitoring during anesthesia is a standard of care, reference ranges for blood pressure in anesthetized children are not available. We developed sex- and age-specific reference ranges for NIBP in children during anesthesia and surgery. METHODS: In this retrospective observational cohort study, we included NIBP data of children with no or mild comorbidity younger than 18 yr old from the Multicenter Perioperative Outcomes Group data set. Sex-specific percentiles of the NIBP values for age were developed and extrapolated into diagrams and reference tables representing the 50th percentile (0 SD), +1 SD, -1 SD, and the upper (+2 SD) and lower reference ranges (-2 SD). RESULTS: In total, 116,362 cases from 10 centers were available for the construction of NIBP age- and sex-specific reference curves. The 0 SD of the mean NIBP during anesthesia varied from 33 mmHg at birth to 67 mmHg at 18 yr. The low cutoff NIBP (2 SD below the 50th percentile) varied from 17 mmHg at birth to 47 mmHg at 18 yr old. CONCLUSIONS: This is the first study to present reference ranges for blood pressure in children during anesthesia. These reference ranges based on the variation of values obtained in daily care in children during anesthesia could be used for rapid screening of changes in blood pressure during anesthesia and may provide a consistent reference for future blood pressure-related pediatric anesthesia research.

Single-center large-cohort study into quality of life in Dutch intensive care unit subgroups, 1 year after admission, using EuroQoL EQ-6D-3L.

PURPOSE: The goal of this study was to describe long-term survival and health-related quality of life (HRQoL), measured by EQ-6D, in a general intensive care unit (ICU) population. MATERIALS AND METHODS: We included 5934 consecutive adult patients admitted to a mixed-population ICU. There were no exclusion criteria. One-year survival status was determined using the Dutch municipal population register. Subsequently, all survivors received the EuroQoL EQ-6D-3L questionnaire. The primary outcome was overall HRQoL and survival of the ICU survivors, compared to overall QoL of an age- and sex-matched reference population. RESULTS: A total of 5138 patients (86.6%) survived until hospital discharge, with 4647 (78.3%) patients surviving the 1-year of follow-up. The EuroQoL questionnaire was sent to 4465 survivors and returned by 3034 (68.0%) of 4465. The median HRQoL in surviving patients was 0.83 (interquartile range [IQR], 0.64-1.00) vs 0.86 (IQR, 0.85-0.86) in the reference population (P < .001). There was marked variation across admission diagnosis groups: cardiac surgery patients had an HRQoL of 0.94 (IQR, 0.74-1.00), whereas patients admitted with chronic renal failure had an HRQoL of 0.65 (IQR, 0.47-0.83). CONCLUSIONS: One year after ICU admission, HRQoL was significantly lower than in the reference population. Notably, marked variations were found across subgroups.

Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study.

INTRODUCTION: Delirium is associated with impaired outcome, but it is unclear whether this relationship is limited to in-hospital outcomes and whether this relationship is independent of the severity of underlying conditions. The aim of this study was to investigate the association between delirium in the intensive care unit (ICU) and long-term mortality, self-reported health-related quality of life (HRQoL), and self-reported problems with cognitive functioning in survivors of critical illness, taking severity of illness at baseline and throughout ICU stay into account. METHODS: A prospective cohort study was conducted. We included patients who survived an ICU stay of at least a day; exclusions were neurocritical care patients and patients who sustained deep sedation during the entire ICU stay. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM-ICU) and additionally, patients who received haloperidol were considered delirious. Twelve months after ICU admission, data on mortality were obtained and HRQoL and cognitive functioning were measured with the European Quality of Life - Six dimensions self-classifier (EQ-6D). Regression analyses were used to assess the associations between delirium and the outcome measures adjusted for gender, type of admission, the Acute Physiology And Chronic Health Evaluation IV (APACHE IV) score, and the cumulative Sequential Organ Failure Assessment (SOFA) score throughout ICU stay. RESULTS: Of 1101 survivors of critical illness, 412 persons (37%) had been delirious during ICU stay, and 198 (18%) died within twelve months. When correcting for confounders, no significant association between delirium and long-term mortality was found (hazard ratio: 1.26; 95% confidence interval (CI) 0.93 to 1.71). In multivariable analysis, delirium was not associated with HRQoL either (regression coefficient: -0.04; 95% CI -0.10 to 0.01). Yet, delirium remained associated with mild and severe problems with cognitive functioning in multivariable analysis (odds ratios: 2.41; 95% CI 1.57 to 3.69 and 3.10; 95% CI 1.10 to 8.74, respectively). CONCLUSIONS: In this group of survivors of critical illness, delirium during ICU stay was not associated with long-term mortality or HRQoL after adjusting for confounding, including severity of illness throughout ICU stay. In contrast, delirium appears to be an independent risk factor for long-term self-reported problems with cognitive functioning.