Post-anesthesia care unit hypotension in low-risk patients recovering from non-cardiac surgery: a prospective observational study.

Intraoperative hypotension is common and associated with organ injury. Hypotension can not only occur during surgery, but also thereafter. After surgery, most patients are treated in post-anesthesia care units (PACU). The incidence of PACU hypotension is largely unknown - presumably in part because arterial pressure is usually monitored intermittently in PACU patients. We therefore aimed to evaluate the incidence, duration, and severity of PACU hypotension in low-risk patients recovering from non-cardiac surgery. In this observational study, we performed blinded continuous non-invasive arterial pressure monitoring with finger-cuffs (ClearSight system; Edwards Lifesciences, Irvine, CA, USA) in 100 patients recovering from non-cardiac surgery in the PACU. We defined PACU hypotension as a mean arterial pressure (MAP) < 65 mmHg. Patients had continuous finger-cuff monitoring for a median (25th percentile, 75th percentile) of 64 (44 to 91) minutes. Only three patients (3%) had PACU hypotension for at least one consecutive minute. These three patients had 4, 4, and 2 cumulative minutes of PACU hypotension; areas under a MAP of 65 mmHg of 17, 9, and 9 mmHg x minute; and time-weighted averages MAP less than 65 mmHg of 0.5, 0.3, and 0.2 mmHg. The median volume of crystalloid fluid patients were given during PACU treatment was 200 (100 to 400) ml. None was given colloids or a vasopressor during PACU treatment. In low-risk patients recovering from non-cardiac surgery, the incidence of PACU hypotension was very low and the few episodes of PACU hypotension were short and of modest severity.

Processed electroencephalography-guided general anesthesia and norepinephrine requirements: A randomized trial in patients having vascular surgery.

STUDY OBJECTIVE: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. DESIGN: Randomized controlled clinical trial. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 110 patients having vascular surgery. INTERVENTIONS: pEEG-guided general anesthesia. MEASUREMENTS: Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. MAIN RESULT: 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 µg kg-1 min-1 in patients assigned to pEEG-guided and 0.12 ± 0.09 µg kg-1 min-1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 µg kg-1 min-1, 95% confidence interval 0.01 to 0.07 µg kg-1 min-1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). CONCLUSION: pEEG-guided - compared to non-pEEG-guided - general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials.

Energy Expenditure Under General Anesthesia: An Observational Study Using Indirect Calorimetry in Patients Having Noncardiac Surgery.

BACKGROUND: Perioperative hemodynamic management aims to optimize organ perfusion pressure and blood flow-assuming this ensures that oxygen delivery meets cellular metabolic needs. Cellular metabolic needs are reflected by energy expenditure. A better understanding of energy expenditure under general anesthesia could help tailor perioperative hemodynamic management to actual demands. We thus sought to assess energy expenditure under general anesthesia. Our primary hypothesis was that energy expenditure under general anesthesia is lower than preoperative awake resting energy expenditure. METHODS: We conducted an observational study on patients having elective noncardiac surgery at the University Medical Center Hamburg-Eppendorf (Germany) between September 2019 and March 2020. We assessed preoperative awake resting energy expenditure, energy expenditure under general anesthesia, and energy expenditure after surgery using indirect calorimetry. We compared energy expenditure under general anesthesia at incision to preoperative awake resting energy expenditure using a Wilcoxon signed-rank test for paired measurements. RESULTS: We analyzed 60 patients. Median (95% confidence interval [CI]) preoperative awake resting energy expenditure was 953 (95% CI, 906-962) kcal d -1 m -2 . Median energy expenditure under general anesthesia was 680 (95% CI, 642-711) kcal d -1 m -2 -and thus 263 (95% CI, 223-307) kcal d -1 m -2 or 27% (95% CI, 23%-30%) lower than preoperative awake resting energy expenditure ( P < .001). CONCLUSIONS: Median energy expenditure under general anesthesia is about one-quarter lower than preoperative awake resting energy expenditure in patients having noncardiac surgery.

A new noninvasive finger sensor (NICCI system) for cardiac output monitoring: A method comparison study in patients after cardiac surgery.

BACKGROUND: The new noninvasive finger sensor system NICCI (Getinge; Gothenburg, Sweden) allows continuous cardiac output monitoring. We aimed to investigate its cardiac output measurement performance. OBJECTIVES: To investigate the NICCI system's cardiac output measurement performance. DESIGN: Prospective method comparison study. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: Fifty-one patients after cardiac surgery. MAIN OUTCOME MEASURES: We performed a method comparison study in 51 patients after cardiac surgery to compare NICCI cardiac output (CO NICCI ) and NICCI cardiac output calibrated to pulmonary artery thermodilution cardiac output measurement (CO NICCI-CAL ) with pulmonary artery thermodilution cardiac output (CO PAT ). As a secondary analysis we also compared CNAP cardiac output (CO CNAP ) and externally calibrated CNAP cardiac output (CO CNAP-CAL ) with CO PAT . RESULTS: We analysed 299 cardiac output measurement pairs. The mean of the differences (95% limits of agreement) between CO NICCI and CO PAT was 0.6 (-1.8 to 3.1) l min -1 with a percentage error of 48%. The mean of the differences between CO NICCI-CAL and CO PAT was -0.4 (-1.9 to 1.1) l min -1 with a percentage error of 29%. The mean of the differences between CO CNAP and CO PAT was 1.0 (-1.8 to 3.8) l min -1 with a percentage error of 53%. The mean of the differences between CO CNAP-CAL and CO PAT was -0.2 (-2.0 to 1.6) l min -1 with a percentage error of 35%. CONCLUSION: The agreement between CO NICCI and CO PAT is not clinically acceptable. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register (DRKS00023189) after inclusion of the first patient on October 2, 2020.

Chronic arterial hypertension and nocturnal non-dipping predict postinduction and intraoperative hypotension: A secondary analysis of a prospective study.

STUDY OBJECTIVE: Postinduction and intraoperative hypotension are associated with organ injury in non-cardiac surgery patients. Automated ambulatory blood pressure monitoring can identify chronic arterial hypertension and nocturnal blood pressure non-dipping. We tested the hypotheses that: a) chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension; and b) adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information. DESIGN: Prediction model development based on a secondary analysis of a prospective observational study. SETTING: German university medical center. PATIENTS: 366 non-cardiac surgery patients who had preoperative automated ambulatory blood pressure monitoring. MEASUREMENTS: Multivariable analyses to identify risk factors for postinduction and intraoperative hypotension. Area under receiver operating characteristics curves (AUROC) and likelihood-ratio tests to test whether adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information. MAIN RESULTS: Risk factors for postinduction hypotension were age in years (odds ratio: 1.06 (95% confidence interval: 1.03 to 1.10), P = 0.001), American Society of Anesthesiologists physical status class (1.85 (1.02 to 3.35), P = 0.043), preoperative use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (15.19 (1.76 to 131.46), P = 0.013), chronic arterial hypertension (2.54 (1.49 to 4.34), P = 0.001), and nocturnal non-dipping (3.61 (2.09 to 6.23), P < 0.001). The model's AUROC was 0.76 (95% confidence interval: 0.71 to 0.81) with and 0.67 (0.62 to 0.73) without information on chronic arterial hypertension and nocturnal non-dipping (P < 0.001). Risk factors for intraoperative hypotension were male sex (1.73 (1.07 to 2.80), P = 0.025), chronic arterial hypertension (4.35 (2.33 to 8.14), P < 0.001), and nocturnal non-dipping (3.56 (2.07 to 6.11), P < 0.001). The model's AUROC was 0.76 (0.70 to 0.81) with and 0.63 (0.57 to 0.69) without information on chronic arterial hypertension and nocturnal non-dipping (P < 0.001). CONCLUSIONS: Chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension in non-cardiac surgery patients. Adding information on chronic arterial hypertension and nocturnal non-dipping moderately improved hypotension prediction models based on preoperative clinical information.

The Relation Between Mean Arterial Pressure and Cardiac Index in Major Abdominal Surgery Patients: A Prospective Observational Cohort Study.

BACKGROUND: Cardiac output is an important hemodynamic variable and determines oxygen delivery. In contrast to blood pressure, cardiac output is rarely measured even in high-risk surgical patients, suggesting that clinicians consider blood pressure to be a reasonable indicator of systemic blood flow. However, the relationship depends on constant vascular tone and volume, both of which routinely vary during anesthesia and surgery. We therefore tested the hypothesis that there is no clinically meaningful correlation between mean arterial pressure and cardiac index in major abdominal surgery patients. METHODS: In this prospective observational study, we assessed the relationship between mean arterial pressure and cardiac index in 100 patients having major abdominal surgery under general anesthesia. RESULTS: The pooled within-patient correlation coefficient calculated using meta-analysis methods was r = 0.34 (95% confidence interval, 0.28-0.40). Linear regression using a linear mixed effects model of cardiac index on mean arterial pressure revealed that cardiac index increases by 0.014 L·min-1·m-2 for each 1 mm Hg increase in mean arterial pressure. The 95% Wald confidence interval of this slope was 0.011 to 0.018 L·min-1·m-2·mm Hg-1 and thus within predefined equivalence margins of -0.03 and 0.03 L·min-1·m-2·mm Hg-1, thereby demonstrating lack of clinically meaningful association between mean arterial pressure and cardiac index. CONCLUSIONS: There is no clinically meaningful correlation between mean arterial pressure and cardiac index in patients having major abdominal surgery. Intraoperative blood pressure is thus a poor surrogate for cardiac index.

Mechanisms contributing to hypotension after anesthetic induction with sufentanil, propofol, and rocuronium: a prospective observational study.

It remains unclear whether reduced myocardial contractility, venous dilation with decreased venous return, or arterial dilation with reduced systemic vascular resistance contribute most to hypotension after induction of general anesthesia. We sought to assess the relative contribution of various hemodynamic mechanisms to hypotension after induction of general anesthesia with sufentanil, propofol, and rocuronium. In this prospective observational study, we continuously recorded hemodynamic variables during anesthetic induction using a finger-cuff method in 92 non-cardiac surgery patients. After sufentanil administration, there was no clinically important change in arterial pressure, but heart rate increased from baseline by 11 (99.89% confidence interval: 7 to 16) bpm (P < 0.001). After administration of propofol, mean arterial pressure decreased by 23 (17 to 28) mmHg and systemic vascular resistance index decreased by 565 (419 to 712) dyn*s*cm-5*m2 (P values < 0.001). Mean arterial pressure was < 65 mmHg in 27 patients (29%). After propofol administration, heart rate returned to baseline, and stroke volume index and cardiac index remained stable. After tracheal intubation, there were no clinically important differences compared to baseline in heart rate, stroke volume index, and cardiac index, but arterial pressure and systemic vascular resistance index remained markedly decreased. Anesthetic induction with sufentanil, propofol, and rocuronium reduced arterial pressure and systemic vascular resistance index. Heart rate, stroke volume index, and cardiac index remained stable. Post-induction hypotension therefore appears to result from arterial dilation with reduced systemic vascular resistance rather than venous dilation or reduced myocardial contractility.

Relationship Between Intraoperative and Preoperative Ambulatory Nighttime Heart Rates: A Secondary Analysis of a Prospective Observational Study.

BACKGROUND: It remains unknown what constitutes physiologically relevant intraoperative bradycardia. Intraoperative bradycardia is usually defined using absolute heart rate thresholds, ignoring preoperative baseline heart rates. In contrast, we considered defining intraoperative bradycardia relative to preoperative ambulatory nighttime heart rate. Specifically, we hypothesized that the individual mean intraoperative heart rate is lower than the mean preoperative ambulatory nighttime heart rate. We, therefore, sought to investigate the relationship between the intraoperative and preoperative ambulatory nighttime heart rates in adults having noncardiac surgery with general anesthesia. Additionally, we sought to investigate the incidence of intraoperative bradycardia using relative versus absolute heart rate thresholds. METHODS: We conducted a secondary analysis of a database from a prospective study including preoperative ambulatory and intraoperative heart rates in 363 patients having noncardiac surgery with general anesthesia. RESULTS: The mean intraoperative heart rate was lower than the mean nighttime heart rate (mean difference, -9 bpm; 95% confidence interval [CI], -10 to -8 bpm; P < .001). The mean intraoperative heart rate was lower than the mean nighttime heart rate in 319 of 363 patients (88%; 95% CI, 84%-91%). The incidence of intraoperative bradycardia was 42% (95% CI, 38%-47%) when it was defined as intraoperative heart rate >30% lower than mean nighttime heart rate and 43% (95% CI, 38%-49%) when it was defined as intraoperative heart rate <45 bpm. CONCLUSIONS: The mean intraoperative heart rate is lower than the mean nighttime heart rate in about 9 of 10 patients. Intraoperative bradycardia might thus be physiologically and clinically important. Future research needs to investigate whether there is an association between intraoperative bradycardia and postoperative outcomes.

Non-invasive measurement of pulse pressure variation using a finger-cuff method in obese patients having laparoscopic bariatric surgery.

Pulse pressure variation (PPV) is a dynamic cardiac preload variable used to predict fluid responsiveness. PPV can be measured non-invasively using innovative finger-cuff systems allowing for continuous arterial pressure waveform recording, e.g., the Nexfin system [BMEYE B.V., Amsterdam, The Netherlands; now Clearsight (Edwards Lifesciences, Irvine, CA, USA)] (PPVFinger). However, the agreement between PPVFinger and PPV derived from an arterial catheter (PPVART) in obese patients having laparoscopic bariatric surgery is unknown. We compared PPVFinger and PPVART at 6 time points in 60 obese patients having laparoscopic bariatric surgery in a secondary analysis of a prospective method comparison study. We used Bland-Altman analysis to assess absolute agreement between PPVFinger and PPVART. The predictive agreement for fluid responsiveness between PPVFinger and PPVART was evaluated across three PPV categories (PPV < 9%, PPV 9-13%, PPV > 13%) as concordance rate of paired measurements and Cohen's kappa. The overall mean of the differences between PPVFinger and PPVART was 0.5 ± 4.6% (95%-LoA - 8.6 to 9.6%) and the overall predictive agreement was 72.4% with a Cohen's kappa of 0.53. The mean of the differences was - 0.7 ± 3.8% (95%-LoA - 8.1 to 6.7%) without pneumoperitoneum in horizontal position and 1.1 ± 4.8% (95%-LoA - 8.4 to 10.5%) during pneumoperitoneum in reverse-Trendelenburg position. The absolute agreement and predictive agreement between PPVFinger and PPVART are moderate in obese patients having laparoscopic bariatric surgery.

Estimation of pulse pressure variation and cardiac output in patients having major abdominal surgery: a comparison between a mobile application for snapshot pulse wave analysis and invasive pulse wave analysis.

Pulse pressure variation (PPV) and cardiac output (CO) can guide perioperative fluid management. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a mobile application for snapshot pulse wave analysis (PWAsnap) and estimates PPV and CO using pulse wave analysis of a snapshot of the arterial blood pressure waveform displayed on any patient monitor. We evaluated the PPV and CO measurement performance of PWAsnap in adults having major abdominal surgery. In a prospective study, we simultaneously measured PPV and CO using PWAsnap installed on a tablet computer (PPVPWAsnap, COPWAsnap) and using invasive internally calibrated pulse wave analysis (ProAQT; Pulsion Medical Systems, Feldkirchen, Germany; PPVProAQT, COProAQT). We determined the diagnostic accuracy of PPVPWAsnap in comparison to PPVProAQT according to three predefined PPV categories and by computing Cohen's kappa coefficient. We compared COProAQT and COPWAsnap using Bland-Altman analysis, the percentage error, and four quadrant plot/concordance rate analysis to determine trending ability. We analyzed 190 paired PPV and CO measurements from 38 patients. The overall diagnostic agreement between PPVPWAsnap and PPVProAQT across the three predefined PPV categories was 64.7% with a Cohen's kappa coefficient of 0.45. The mean (± standard deviation) of the differences between COPWAsnap and COProAQT was 0.6 ± 1.3 L min- 1 (95% limits of agreement 3.1 to - 1.9 L min- 1) with a percentage error of 48.7% and a concordance rate of 45.1%. In adults having major abdominal surgery, PPVPWAsnap moderately agrees with PPVProAQT. The absolute and trending agreement between COPWAsnap with COProAQT is poor. Technical improvements are needed before PWAsnap can be recommended for hemodynamic monitoring.

Intraoperative hypotension: Pathophysiology, clinical relevance, and therapeutic approaches.

Intraoperative hypotension (IOH) i.e., low arterial blood pressure (AP) during surgery is common in patients having non-cardiac surgery under general anaesthesia. It has a multifactorial aetiology, and is associated with major postoperative complications including acute kidney injury, myocardial injury and death. Therefore, IOH may be a modifiable risk factor for postoperative complications. However, there is no uniform definition for IOH. IOH not only occurs during surgery but also after the induction of general anaesthesia before surgical incision. However, the optimal therapeutic approach to IOH remains elusive. There is evidence from one small randomised controlled trial that individualising AP targets may reduce the risk of postoperative organ dysfunction compared with standard care. More research is needed to define individual AP harm thresholds, to develop therapeutic strategies to treat and avoid IOH, and to integrate new technologies for continuous AP monitoring.

Predicting hypotension in perioperative and intensive care medicine.

Blood pressure is the main determinant of organ perfusion. Hypotension is common in patients having surgery and in critically ill patients. The severity and duration of hypotension are associated with hypoperfusion and organ dysfunction. Hypotension is mostly treated reactively after low blood pressure values have already occurred. However, prediction of hypotension before it becomes clinically apparent would allow the clinician to treat hypotension pre-emptively, thereby reducing the severity and duration of hypotension. Hypotension can now be predicted minutes before it actually occurs from the blood pressure waveform using machine-learning algorithms that can be trained to detect subtle changes in cardiovascular dynamics preceding clinically apparent hypotension. However, analyzing the complex cardiovascular system is a challenge because cardiovascular physiology is highly interdependent, works within complicated networks, and is influenced by compensatory mechanisms. Improved hemodynamic data collection and integration will be a key to improve current models and develop new hypotension prediction models.

MicroRNA miR-301a is a novel cardiac regulator of Cofilin-2.

Calsarcin-1 deficient mice develop dilated cardiomyopathy (DCM) phenotype in pure C57BL/6 genetic background (Cs1-ko) despite severe contractile dysfunction and robust activation of fetal gene program. Here we performed a microRNA microarray to identify the molecular causes of this cardiac phenotype that revealed the dysregulation of several microRNAs including miR-301a, which was highly downregulated in Cs1-ko mice compared to the wild-type littermates. Cofilin-2 (Cfl2) was identified as one of the potential targets of miR-301a using prediction databases, which we validated by luciferase assay and mutation of predicted binding sites. Furthermore, expression of miR-301a contrastingly regulated Cfl2 expression levels in neonatal rat ventricular cardiomyocytes (NRVCM). Along these lines, Cfl2 was significantly upregulated in Cs1-ko mice, indicating the physiological association between miR-301a and Cfl2 in vivo. Mechanistically, we found that Cfl2 activated serum response factor response element (SRF-RE) driven luciferase activity in neonatal rat cardiomyocytes and in C2C12 cells. Similarly, knockdown of miR301a activated, whereas, its overexpression inhibited the SRF-RE driven luciferase activity, further strengthening physiological interaction between miR-301a and Cfl2. Interestingly, the expression of SRF and its target genes was strikingly increased in Cs1-ko suggesting a possible in vivo correlation between expression levels of Cfl2/miR-301a and SRF activation, which needs to be independently validated. In summary, our data demonstrates that miR-301a regulates Cofilin-2 in vitro in NRVCM, and in vivo in Cs1-ko mice. Our findings provide an additional and important layer of Cfl2 regulation, which we believe has an extended role in cardiac signal transduction and dilated cardiomyopathy presumably due to the reported involvement of Cfl2 in these mechanisms.

Myeloid leukemia factor-1 is a novel modulator of neonatal rat cardiomyocyte proliferation.

The present study focuses on the identification of the gene expression profile of neonatal rat cardiomyocytes (NRVCMs) after dynamic mechanical stretch through microarrays of RNA isolated from cells stretched for 2, 6 or 24h. In this analysis, myeloid leukemia factor-1 (MLF1) was found to be significantly downregulated during the course of stretch. We found that MLF1 is highly expressed in the heart, however, its cardiac function is unknown yet. In line with microarray data, MLF1 was profoundly downregulated in in vivo mouse models of cardiomyopathy, and also significantly reduced in the hearts of human patients with dilated cardiomyopathy. Our data indicates that the overexpression of MLF1 in NRVCMs inhibited cell proliferation while augmenting apoptosis. Conversely, knockdown of MLF1 protected NRVCMs from apoptosis and promoted cell proliferation. Moreover, we found that knockdown of MLF1 protected NRVCMs from hypoxia-induced cell death. The observed accelerated apoptosis is attributed to the activation of caspase-3/-7/PARP-dependent apoptotic signaling and upregulation of p53. Most interestingly, MLF1 knockdown significantly upregulated the expression of D cyclins suggesting its possible role in cyclin-dependent cell proliferation. Taken together, we, for the first time, identified an important role for MLF1 in NRVCM proliferation.