Postoperative Hypotension after Noncardiac Surgery and the Association with Myocardial Injury.

BACKGROUND: Intraoperative hypotension has been associated with postoperative morbidity and early mortality. Postoperative hypotension, however, has been less studied. This study examines postoperative hypotension, hypothesizing that both the degree of hypotension severity and longer durations would be associated with myocardial injury. METHODS: This single-center observational cohort was comprised of 1,710 patients aged 60 yr or more undergoing intermediate- to high-risk noncardiac surgery. Frequent sampling of hemodynamic monitoring on a postoperative high-dependency ward during the first 24 h after surgery was recorded. Multiple mean arterial pressure (MAP) absolute thresholds (50 to 75 mmHg) were used to define hypotension characterized by cumulative minutes, duration, area, and time-weighted-average under MAP. Zero time spent under a threshold was used as the reference group. The primary outcome was myocardial injury (a peak high-sensitive troponin T measurement 50 ng/l or greater) during the first 3 postoperative days. RESULTS: Postoperative hypotension was common, e.g., 2 cumulative hours below a threshold of 60 mmHg occurred in 144 (8%) patients while 4 h less than 75 mmHg occurred in 824 (48%) patients. Patients with myocardial injury had higher prolonged exposures for all characterizations. After adjusting for confounders, postoperative duration below a threshold of 75 mmHg for more than 635 min was associated with myocardial injury (adjusted odds ratio, 2.68; 95% CI, 1.46 to 5.07, P = 0.002). Comparing multiple thresholds, cumulative durations of 2 to 4 h below a MAP threshold of 60 mmHg (adjusted odds ratio, 3.26; 95% CI, 1.57 to 6.48, P = 0.001) and durations of more than 4 h less than 65 mmHg (adjusted odds ratio, 2.98; 95% CI, 1.78 to 4.98, P < 0.001) and 70 mmHg (adjusted odds ratio, 2.18; 95% CI, 1.37 to 3.51, P < 0.001) were also associated with myocardial injury. Associations remained significant after adjusting for intraoperative hypotension, which independently was not associated with myocardial injury. CONCLUSIONS: In this study, postoperative hypotension was common and was independently associated with myocardial injury.

Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux.

BACKGROUND: Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. METHODS: Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety-Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. RESULTS: Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from -0.38 (2.18) to -2.41(2.43) µmol min 100 g. CONCLUSIONS: Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Cerebral perfusion pressure in women with preeclampsia is elevated even after treatment of elevated blood pressure.

Cerebral perfusion pressure (CPP) is elevated in preeclampsia, and may predispose to cerebrovascular complications and progression to eclampsia. We estimated zero flow pressure (ZFP) and CPP using simultaneously obtained arterial blood pressure and middle cerebral artery blood flow velocity in 10 women with preeclampsia, all treated with methyldopa with or without nifedipine, and 18 healthy pregnant controls. Mean ± SD ZFP was lower in women with preeclampsia than in controls (16.8 ± 10.9 vs. 31.7 ± 15.0 mmHg, p = 0.01) whereas CPP was considerably higher (82.3 ± 17.7 vs. 55.0 ± 11.7 mmHg, p < 0.001), as was the cerebral flow index (41.9 ± 18.0 vs. 25.6 ± 11.2, p = 0.02). There was a significant correlation between blood pressure and CPP in women with preeclampsia, but not in controls. Women with preeclampsia may have an increased cerebral perfusion due to a reduced ZFP and increased CPP despite treatment with antihypertensive medication. More rigorous antihypertensive therapy, aimed at reducing CPP, could result in a decrease in cerebral complications in women with preeclampsia.

Lorazepam does not improve the quality of recovery in day-case surgery patients: a randomised placebo-controlled clinical trial.

BACKGROUND: In day-case surgery, the effects of the anxiolytic lorazepam as premedication on the quality of postoperative recovery are unknown. OBJECTIVE: To evaluate whether lorazepam as a premedication beneficially affects quality of recovery (primary outcome) and psychological manifestations (secondary outcome) after day-case surgery. DESIGN: A randomised, double-blind, placebo-controlled clinical trial. SETTING: Single tertiary centre. INCLUSION CRITERIA: day-case surgery; age at least 18 years. EXCLUSION CRITERIA: insufficient knowledge of the Dutch language; intellectual disability; ophthalmology surgery; extracorporeal shock wave lithotripsy; endoscopy; botulinum toxin A treatment; abortion; chronic pain treatment; preceding use of psychopharmaceuticals; contraindication to lorazepam. INTERVENTION: Lorazepam (1 to 1.5 mg) intravenously vs. NaCl 0.9% as a premedication prior to surgery. MAIN OUTCOME MEASURE: Quality of Recovery-40 (QoR-40) score. SECONDARY OUTCOMES: State-Trait Anxiety Inventory (STAI-State/Trait); State-Trait Anger Scale (STAS-State/Trait); Multidimensional Fatigue Inventory (MFI); Hospital Anxiety and Depression Scale (HADS). Timing of evaluation: T0: preoperatively (all scales); T1: before discharge (STAI-State/Trait); T2: first postoperative working day (QoR-40); T3: 7th day after surgery (all scales). Robust regression analysis was applied. Statistical analyses were adjusted for the corresponding baseline value and sex. RESULTS: Four hundred patients were randomised; 398 patients were analysed. Postoperative mean QoR-40 scores were similar in both groups at T2 (174.5 vs. 176.4, P = 0.34) and T3 (172.8 vs.176.3, P = 0.38). Postoperative mean STAI-State/Trait scores decreased less in the group with lorazepam at T1 (32.3 vs. 29.3, P < 0.0001; 32.7 vs. 30.8, P = 0.0002). STAI-Trait and HADS-Anxiety decreased less in the group with lorazepam at T3 (31.1 vs. 30.0; P = 0.03, 3.3 vs. 2.5, P = 0.003). STAS-State increased in the group with lorazepam at T3 (10.8 vs. 10.3, P = 0.04). CONCLUSION: In day-case surgery, lorazepam as a premedication did not improve quality of recovery. Furthermore, this premedication may delay the decrease in postoperative anxiety and aggression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01441843.

Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial.

BACKGROUND: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload.In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements. METHODS/DESIGN: This is a double blind, multicenter, placebo-controlled randomized trial.Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements. DISCUSSION: Patients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and transfusion will not affect the volume status prior to the surgical procedure. We hypothesize that administration of prothrombin complex concentrate will result in a reduction of perioperative blood loss and transfusion requirements. Theoretically, the administration of prothrombin complex concentrate may be associated with a higher risk of thromboembolic complications. Therefore, thromboembolic complications are an important secondary endpoint and the occurrence of this type of complication will be closely monitored during the study. TRIAL REGISTRATION: The trial is registered at http://www.trialregister.nl with number NTR3174. This registry is accepted by the ICMJE.

Preoperative risk assessment and prevention of complications in patients with esophageal cancer.

In this review the preoperative risk assessment and prevention of complications in patients undergoing esophagectomy for cancer is discussed. Age, pulmonary and cardiovascular condition, nutritional status, and neoadjuvant chemo(radio)therapy are known predictive factors. None of these factors is a valid exclusion criterion for esophagectomy, but may help in careful patient selection. Both anesthetists and surgeons play an important role in intraoperative risk reduction by means of appropriate fluid management and application of optimal surgical techniques.

Effective Cerebral Perfusion Pressure: Does the Estimation Method Make a Difference?

INTRODUCTION: The effective cerebral perfusion pressure (CPPe), zero-flow pressure (ZFP), and resistance area product (RAP) are important determinants of cerebral blood flow. ZFP and RAP are usually estimated by linear regression analysis of pressure-velocity relationships of the middle cerebral artery. The aim of this study was to validate 4 other estimation methods against the standard linear regression method. METHODS: In a previous study, electroencephalography, arterial blood pressure, and middle cerebral artery flow velocity were measured in patients during internal cardioverter defibrillator implantation procedures to determine the electroencephalography frequency ranges that represent ischemic changes during periods of circulatory arrest. In this secondary analysis, arterial blood pressure and middle cerebral artery flow velocity were used to estimate CPPe, ZFP, and RAP by 4 different methods-the 3-point intercept calculation (LR3, systolic/mean/diastolic) and methods described by Czosnyka (systolic/diastolic), Belford (mean/diastolic), and Schmidt (systolic/diastolic)-and compare them with the reference linear regression method. CPPe was calculated as the difference between mean arterial pressure and ZFP. The primary endpoint was the difference, correlation, and agreement of these differently estimated CPPe measurements. RESULTS: In total, 174 measurements in 35 patients were collected under steady-state conditions before the first circulatory arrest phase during internal cardioverter defibrillator testing. CPPe, ZFP, and RAP measurements based on the 3-point intercept and Czosnyka calculation methods showed small mean differences, good agreement, low percentage errors, and excellent correlation when compared with the reference method. Agreement and correlation were moderate for the Belford method and unsatisfactory for the Schmidt method. CONCLUSIONS: CPPe, ZFP, and RAP measurements based on 2 alternative calculation methods are comparable to the linear regression reference method.

Small intra-individual variability of the pre-ejection period justifies the use of pulse transit time as approximation of the vascular transit.

BACKGROUND: Vascular transit time (VTT) is the propagation time of a pulse wave through an artery; it is a measure for arterial stiffness. Because reliable non-invasive VTT measurements are difficult, as an alternative we measure pulse transit time (PTT). PTT is defined as the time between the R-wave on electrocardiogram and arrival of the resulting pulse wave in a distal location measured with photoplethysmography (PPG). The time between electrical activation of the ventricles and the resulting pulse wave after opening of the aortic valve is called the pre-ejection period (PEP), a component of PTT. The aim of this study was to estimate the variability of PEP at rest, to establish how accurate PTT is as approximation of VTT. METHODS: PTT was measured and PEP was assessed with echocardiography (gold standard) in three groups of 20 volunteers: 1) a control group without cardiovascular disease aged <50 years and 2) aged >50 years, and 3) a group with cardiovascular risk factors, defined as arterial hypertension, dyslipidemia, kidney failure and diabetes mellitus. RESULTS: Per group, the mean PEP was: 1) 58.5 ± 13.0 ms, 2) 52.4 ± 11.9 ms, and 3) 57.6 ± 11.6 ms. However, per individual the standard deviation was much smaller, i.e. 1) 2.0-5.9 ms, 2) 2.8-5.1 ms, and 3) 1.6-12.0 ms, respectively. There was no significant difference in the mean PEP of the 3 groups (p = 0.236). CONCLUSION: In conclusion, the intra-individual variability of PEP is small. A change in PTT in a person at rest is most probably the result of a change in VTT rather than of PEP. Thus, PTT at rest is an easy, non-invasive and accurate approximation of VTT for monitoring arterial stiffness.

Argon does not affect cerebral circulation or metabolism in male humans.

OBJECTIVE: Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. MATERIALS AND METHODS: In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. RESULTS: Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. DISCUSSION: Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia.

Surgery for a large tracheoesophageal fistula using extracorporeal membrane oxygenation.

We report a patient with a giant tracheoesophageal fistula (TEF) planned for reconstructive surgery. Because mechanical ventilation in any form was technically impossible, we successfully used veno-venous extracorporeal membrane oxygenation (VV-ECMO) without the need for mechanical ventilation.

One-Year Follow-Up After Hybrid Thoracoabdominal Aortic Repair.

BACKGROUND: Compared to open thoracoabdominal aortic aneurysm (TAAA) repair, hybrid repair is thought to be less invasive with better perioperative outcomes. Due to the extent of the operation and long recovery period, studying perioperative results may not be sufficient for evaluation of the true treatment effect. The aim of this study is to evaluate 1-year mortality and morbidity in patients with TAAA undergoing hybrid repair. METHODS: In a retrospective cohort study, all medical records of patients undergoing hybrid repair for TAAA at the Erasmus University Medical Center between January 2007 and January 2015 were studied. Primary outcome measures were 30-day and 1-year mortality. Secondary outcome measures included major in-hospital postoperative complications. RESULTS: A total of 15 patients were included. All-cause mortality was 33% (5 of the 15) at 30 days and 60% (9 of the 15) at 1 year. Aneurysm-related mortality was 33% (5 of the 15) and 53% (8 of the 15) at 30-day and 1-year follow-up, respectively, with colon ischemia being the most common cause of death. Major complication rate was high: myocardial infarction in 2 (13%) cases, acute kidney failure in 5 (33%) cases, bowel ischemia in 3 (20%) cases, and spinal cord ischemia in 1 (7%) case. CONCLUSION: The presumed less invasive nature of hybrid TAAA repair does not seem to result in lower complication rates. The high mortality rate at 30 days continues to rise dramatically thereafter, suggesting that 1-year mortality is a more useful clinical parameter to use in preoperative decision-making for this kind of repair.

Influence of isoflurane on the diastolic pressure-flow relationship and critical occlusion pressure during arterial CABG surgery: a randomized controlled trial.

The effects of isoflurane on the determinants of blood flow during Coronary Artery Bypass Graft (CABG) surgery are not completely understood. This study characterized the influence of isoflurane on the diastolic Pressure-Flow (P-F) relationship and Critical Occlusion Pressure (COP) during CABG surgery. Twenty patients undergoing CABG surgery were studied. Patients were assigned to an isoflurane or control group. Hemodynamic and flow measurements during CABG surgery were performed twice (15 minutes after the discontinuation of extracorporeal circulation (T15) and again 15 minutes later (T30)). The zero flow pressure intercept (a measure of COP) was extrapolated from a linear regression analysis of the instantaneous diastolic P-F relationship. In the isoflurane group, the application of isoflurane significantly increased the slope of the diastolic P-F relationship by 215% indicating a mean reduction of Coronary Vascular Resistance (CVR) by 46%. Simultaneously, the Mean Diastolic Aortic Pressure (MDAP) decreased by 19% mainly due to a decrease in the systemic vascular resistance index by 21%. The COP, cardiac index, heart rate, Left Ventricular End-Diastolic Pressure (LVEDP) and Coronary Sinus Pressure (CSP) did not change significantly. In the control group, the parameters remained unchanged. In both groups, COP significantly exceeded the CSP and LVEDP at both time points. We conclude that short-term application of isoflurane at a sedative concentration markedly increases the slope of the instantaneous diastolic P-F relationship during CABG surgery implying a distinct decrease with CVR in patients undergoing CABG surgery.

Carbon dioxide induced changes in cerebral blood flow and flow velocity: role of cerebrovascular resistance and effective cerebral perfusion pressure.

In addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe) and the resistance area product (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the interrelationship of PaCO2-induced changes in CBF, CVR, CPPe, ZFP, and RAP is not fully understood. In a controlled crossover trial, we investigated 10 anesthetized patients aiming at PaCO2 levels of 30, 37, 43, and 50 mm Hg. Cerebral blood flow was measured with a modified Kety-Schmidt-technique. Zero flow pressure and RAP was estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. Effective cerebral perfusion pressure was calculated as the difference between mean arterial pressure and ZFP, CVR as the ratio CPPe/CBF. Statistical analysis was performed by one-way RM-ANOVA. When comparing hypocapnia with hypercapnia, CBF showed a significant exponential reduction by 55% and mean VMCA by 41%. Effective cerebral perfusion pressure linearly decreased by 17% while ZFP increased from 14 to 29 mm Hg. Cerebrovascular resistance increased by 96% and RAP by 39%; despite these concordant changes in mean CVR and Doppler-derived RAP correlation between these variables was weak (r=0.43). In conclusion, under general anesthesia hypocapnia-induced reduction in CBF is caused by both an increase in CVR and a decrease in CPPe, as a consequence of an increase in ZFP.