T. Laitio

Epidural infusion of bupivacaine and fentanyl reduces perioperative myocardial ischaemia in elderly patients with hip fracture--a randomized controlled trial.

Background: Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery. The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture.

Correlation properties and complexity of perioperative RR-interval dynamics in coronary artery bypass surgery patients.

Background Dynamic measures of heart rate variability (HRV) may uncover abnormalities that are not easily detectable with traditional time and frequency domain measures. The purpose of this study was to characterize changes in RR-interval dynamics in the immediate postoperative phase of coronary artery bypass graft (CABG) surgery using traditional and selected newer dynamic measures of HRV. Methods Continuous 24-h electrocardiograph recordings were performed in 40 elective CABG surgery patients up to 72 h postoperatively. In one half of the patients, Holter recordings were initiated 12–40 h before the surgery. Time and frequency domain measures of HRV were assessed. The dynamic measures included a quantitative and visual analysis of Poincaré plots, measurement of short- and intermediate-term fractal-like scaling exponents (&agr;1 and &agr;2), the slope (&bgr;) of the power-law regression line of RR-interval dynamics, and approximate entropy. Results The SD of RR intervals (P < 0.001) and the ultra-low-, very-low-, low-, and high-frequency power (P < 0.01, P < 0.001, P < 0.001, P < 0.01, respectively) measures in the first postoperative 24 h decreased from the preoperative values. Analysis of Poincaré plots revealed increased randomness in beat-to-beat heart rate behavior demonstrated by an increase in the ratio between short-term and long-term HRV (P < 0.001) after CABG. Average scaling exponent &agr;1 of the 3 postoperative days decreased significantly after CABG (from 1.22 ± 0.15 to 0.85 ± 0.20, P < 0.001), indicating increased randomness of short-term heart rate dynamics (i.e., loss of fractal-like heart rate dynamics). Reduced scaling exponent &agr;1 of the first postoperative 24 h was the best HRV measure in differentiating between the patients that had normal (≤ 48 h, n = 33) or prolonged (> 48 h, n = 7) intensive care unit stay (0.85 ± 0.17 vs. 0.68 ± 0.18;P < 0.05). In stepwise multivariate logistic regression analysis including typical clinical predictors, &agr;1 was the most significant independent predictor (P < 0.05) of long intensive care unit stay. None of the preoperative HRV measures were able to predict prolonged intensive care unit stays. Conclusions In the selected group of patients studied, a decrease in overall HRV was associated with altered nonlinear heart rate dynamics after CABG surgery. Current results suggest that a more random short-term heart rate behavior may be associated with a complicated clinical course. Analysis of fractal-like dynamics of heart rate may provide new perspectives in detecting abnormal cardiovascular function after CABG.

The role of heart rate variability in risk stratification for adverse postoperative cardiac events.

There is growing evidence of a strong association between the compromised autonomic nervous system and sudden cardiac death. Heart rate variability (HRV) measures are widely used to measure alterations in the autonomic nervous system. Several studies with cardiac patients show that decreased HRV as well as baroreceptor dysfunction are more powerful predictors for sudden cardiac death than established clinical predictors such as left ventricular ejection fraction. One-third of all postoperative complications and more than half of the deaths are due to cardiac complications. Several risk indices are useful for immediate perioperative short-term, but not for long-term outcome risk stratification of an individual patient. Currently, there are no clinically assimilated methods for long-term postoperative risk assessment. Recently, few studies have shown that preoperatively decreased HRV can independently predict postoperative long-term mortality. Further studies with surgical patients are needed to establish a possible predictive value of preoperative baroreceptor dysfunction, alone and combined with HRV, for short- and long-term postoperative outcome.

Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest.

Objectives:Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. Design:An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892). Setting:A multipurpose ICU in university hospital. Patients:Thirty-six adult out-of-hospital cardiac arrest patients (18–80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm. Interventions:Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n = 18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon + mild therapeutic hypothermia group, n = 18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n = 17; Xenon + mild therapeutic hypothermia group, n = 16). Measurements and Main Results:Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group = 5.30u2009mg vs Xenon + mild therapeutic hypothermia group = 2.95u2009mg, p = 0.06). Heart rate was significantly lower in Xenon + mild therapeutic hypothermia patients during hypothermia (p = 0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon + mild therapeutic hypothermia group (p = 0.04). Conclusions:Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

The breakdown of fractal heart rate dynamics predicts prolonged postoperative myocardial ischemia.

UNLABELLEDnPatients with myocardial ischemia after noncardiac surgery have a three- to ninefold increased risk of adverse cardiac events. In this study we tested the hypothesis that altered preoperative heart rate variability (HRV) predicts postoperative prolonged myocardial ischemia (>10 min) in elderly surgical patients. Thirty-two patients, age 60 yr or older, admitted to hospital for surgical repair of a traumatic hip fracture with preoperative night and daytime Holter recordings were included. Holter monitoring was initiated at arrival at hospital and continued until the third postoperative morning. Conventional HRV measures along with analysis of short-term fractal scaling exponent (alpha(1)) of RR intervals were assessed for night (from 2 AM to 5 AM) and day (7 AM to 12 AM) periods in each patient. Preoperative alpha(1) was significantly lower (i.e., increased randomness in HRV) during the nighttime compared with daytime (mean +/- SEM; 0.92 +/- 0.08 versus 1.03 +/- 0.06; P = 0.002) in patients with postoperative myocardial ischemia. Patients without ischemia had no such difference. In stepwise multivariate logistic regression analysis, increased preoperative night-day difference of alpha(1) was the only independent predictor of postoperative prolonged ischemia. The odds ratio for an increase of 0.16 U in night-day difference of alpha(1) (corresponding to interquartile range) was 7.7 (95% confidence interval, 1.9-51.4; P = 0.0018). Breakdown of fractal-like heart rate dynamics is predictive for postoperative prolonged myocardial ischemia in elderly patients having emergency surgery for traumatic hip fracture.nnnIMPLICATIONSnNight and daytime Holter recordings before surgical repair of traumatic hip fracture were analyzed with linear and nonlinear heart rate variability methods. Preoperatively increased randomness in heart rate variability was predictive for postoperative, silent prolonged myocardial ischemia. Prolonged myocardial ischemia increases the risk for adverse cardiac events.

Relation of heart rate dynamics to the occurrence of myocardial ischemia after coronary artery bypass grafting

Postoperative myocardial ischemia is a common finding after coronary artery bypass grafting (CABG) and is associated with an adverse short-term clinical outcome. The reasons and pathophysiologic background for the occurrence of ischemia after CABG are not well established. We tested the hypothesis that altered heart rate (HR) behavior precedes the onset of myocardial ischemic episodes in patients after CABG. Time-domain HR variability measurements, along with analysis of Poincaré plots and fractal scaling analysis were assessed in 40 CABG patients from 48-hour postoperative Holter recordings. Twenty patients experienced 195 ischemic episodes during the postoperative course. In the univariate analysis of HR variability measurements of the first postoperative day (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR variability analyzed from the Poincaré plot and the decreased short- and intermediate-term fractal scaling exponents alpha(1) and alpha(2) were significantly associated with ischemia during the study period (p <0.01, p <0.05, and p <0.05, respectively). In the multivariate model, the increased SD1/SD2 ratio of the first POD was the most powerful independent predictor of all possible confounding variables for the occurrence of postoperative ischemia (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval 1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial ischemic episodes in patients after CABG, suggesting that the autonomic nervous system has an important role in the pathogenesis of myocardial ischemia in the postoperative phase of CABG.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCEnEvidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies.nnnOBJECTIVEnTo determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI).nnnDESIGN, SETTING, AND PARTICIPANTSnA randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized.nnnINTERVENTIONSnPatients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (nu2009=u200955 in the xenon group) or hypothermia treatment alone (nu2009=u200955 in the control group).nnnMAIN OUTCOMES AND MEASURESnThe primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months.nnnRESULTSnAmong the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], Pu2009=u2009.006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; Pu2009=u2009.68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; Pu2009=u2009.053).nnnCONCLUSIONS AND RELEVANCEnAmong comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00879892.

The effects of surgical levels of sevoflurane and propofol anaesthesia on heart rate variability

BACKGROUND AND OBJECTIVEnWe compared heart rate dynamics during surgical levels of propofol and sevoflurane anaesthesia in a highly standardized setting.nnnMETHODSnWe recorded electrocardiography from 24 anaesthetized healthy male subjects. In the first parallel part of the study, the subjects were anaesthetized either with sevoflurane (n = 8) or propofol (n = 8) targeted to match 1.0, 1.5 and 2.0 minimal alveolar concentration/effective concentration 50. In the second part, a separate group (n = 8) underwent four different anaesthetic regimens targeted to bispectral index 40: sevoflurane alone, sevoflurane + 70% nitrous oxide, propofol alone and propofol + 70% nitrous oxide. The electrocardiography data were analysed using conventional time and frequency domain methods, and the approximate entropy method, which estimates the complexity of the data.nnnRESULTSnThe induction of anaesthesia was followed by an overall reduction of heart rate variability, evident in all frequency bands in the spectral analysis, and also in the time domain measures. Approximate entropy decreased at 1 effective concentration 50 with propofol and at 2 minimal alveolar concentration with sevoflurane. In the second part of the study, the time domain variables and high-frequency spectral power were all similarly reduced by sevoflurane and propofol anaesthesia, with and without nitrous oxide. Approximate entropy tended to decrease during propofol anaesthesia.nnnCONCLUSIONSnHypnotic levels of sevoflurane and propofol anaesthesia suppressed the heart rate variability measured using conventional analysis methods. Deeper surgical levels of anaesthesia also reduce the complexity of heart rate variability.Background and objective: Analgesics and anaesthetics have diverse synaptic actions that nonetheless have a common net inhibitory action on neuronal discharge. It is puzzling, therefore, that these two classes of compounds have fundamentally different affects, one blocking pain and the other consciousness. Indeed, beyond the isolated synapse, little is known of the larger scale mechanisms that mediate actual function, for example, transient neuronal assemblies. It was hypothesized that the two classes of drugs might have, respectively, differential effects on transient activation of these assemblies of neurons working together. Methods: Hippocampal tissue from juvenile Wistar rats was used for in vitro optical imaging with voltage‐sensitive dyes and simultaneous field potential recordings. The response to paired pulse stimulation of the hippocampus was recorded in the presence and absence of two types of analgesic (morphine and gabapentin) and two types of anaesthetic (thiopental and propofol). Results: Optical imaging and electrophysiology used in parallel yield quite different results. Most consistently, the imaging technique was able to detect an enhanced period of activation following anaesthetic, but not analgesic application. This effect was not readily seen from electrophysiology field potential recordings. Conclusions: These findings suggest that, irrespective of the effects of the two drug classes at a synaptic level, the dynamics of transient neuronal assemblies are modified selectively by anaesthetics and not analgesics.

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Importance International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. Objective To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM. Design, Setting, and Participants This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016. Interventions Patients were randomized to TTM (33u2009±u20091°C) for 48 hours (nu2009=u2009176) or 24 hours (nu2009=u2009179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C. Main Outcomes and Measures The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. Results In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, −5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; Pu2009=u2009.33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, −6.5%; 95% CI, −16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; Pu2009=u2009.19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; Pu2009=u2009.22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; Pu2009=u2009.04). The median length of intensive care unit stay (151 vs 117 hours; Pu2009<u2009.001), but not hospital stay (11 vs 12 days; Pu2009=u2009.50), was longer in the 48-hour group than in the 24-hour group. Conclusions and Relevance In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted. Trial Registration clinicaltrials.gov Identifier: NCT01689077

Safety of coronary artery bypass surgery during therapeutic oral anticoagulation

INTRODUCTIONnTherapeutic (international normalized ratio, INR 2.0-3.5) oral anticoagulation (TOAC) is assumed to increase perioperative bleeding complications and a standard recommendation is to discontinue warfarin before coronary bypass grafting (CABG).nnnMATERIALS AND METHODSnTo assess the safety of TOAC we retrospectively analyzed consecutive patients (n=270) with long-term warfarin therapy referred for CABG in two centers where TOAC strategy is employed. The main in-hospital outcomes of interest were death, stroke, acute myocardial infarction, new onset renal failure, resternotomy, and their composite. In the TOAC group of 103 patients CABG was performed during therapeutic oral anticoagulation and in the control group (81 patients) preoperative INR was lowered to a subtherapeutic (≤1.5) level.nnnRESULTSnThe patients in TOAC group were more often operated on an emergency basis (p=0.02) and their EuroSCORE was higher (p=0.02). There were no significant differences in the major outcome events or their composite (17.5 vs. 11.1%, p=0.30) between the groups. Patients in the TOAC group had more postoperative blood loss (941±615 vs. 754±610 ml, p<0.01) and received more fresh frozen plasma (2.8±3.0 vs. 1.3±2.4 units, p<0.001), but transfused red blood cells (2.1±2.8 vs. 2.1±3.4 units) were comparable in the groups. Preoperative clopidogrel (OR 4.8, 95% CI 1.4-16.2, p=0.01) and enoxaparin therapy (OR 2.6, 95% CI 1.1-6.5, p=0.04) were the only significant independent predictors for any major adverse event.nnnCONCLUSIONSnOur study suggests that CABG is a safe procedure during TOAC with no excess bleeding or major complications. Prospective trials are needed to confirm this observation.