Post-resuscitation Intensive Care Research Articles

Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial.

To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure. The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy. Pulmonary artery catheters were inserted shortly after admission. History of heart failure was assessed through chart review of all included patients. The primary outcome was cardiac index during the first 72 hours. Secondary outcomes were left ventricular ejection fraction, heart rate, stroke volume, renal replacement therapy and all-cause mortality at 365 days. A total of 134 patients (17% of the BOX cohort) had a history of heart failure (patients with left ventricular ejection fraction, ≤40%: 103 [77%]) of which 71 (53%) were allocated to a MAP of 77 mm Hg. Cardiac index at intensive care unit arrival was 1.77±0.11 L/min·m-2 in the MAP63-group and 1.78±0.17 L/min·m-2 in the MAP77, P=0.92. During the next 72 hours, the mean difference was 0.15 (95% CI, -0.04 to 0.35) L/min·m-2; Pgroup=0.22. Left ventricular ejection fraction and stroke volume was similar between the groups. Patients allocated to MAP77 had significantly elevated heart rate (mean difference 6 [1-12] beats/min, Pgroup=0.03). Vasopressor usage was also significantly increased (P=0.006). At 365 days, 69 (51%) of the patients had died. The adjusted hazard ratio for 365 day mortality was 1.38 (0.84-2.27), P=0.20 and adjusted odds ratio for renal replacement therapy was 2.73 (0.84-8.89; P=0.09). In resuscitated patients with out-of-hospital cardiac arrest with a history of heart failure, allocation to a higher blood pressure target resulted in significantly increased heart rate in the higher blood pressure-target group. However, no certain differences was found for cardiac index, left ventricular ejection fraction or stroke volume. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.

Asphyxial Circulatory Arrest with a Complex of Resuscitation Measures in an Experimental Model

The majority of asphyxial circulatory arrest (CA) models have a number of disadvantages, such as the lack of uniform criteria for fixing CA and recovery of spontaneous circulation, short duration of CA episode and limited volume of post-resuscitation intensive care, poor similarity with resuscitation measures in current clinical anesthesiology/intensive care settings.The aim of the study: to improve the experimental model of asphyxicial CA by standardizing experimental procedures and using a complex of resuscitation measures replicating current CA management in clinical anesthesiology-intensive care.Materials and methods. The experiments were conducted on 34 male Wistar rats, distributed into 2 groups: Group I included animals subjected to sham procedure (SP, N=12) and Group II – animals subjected to asphyxial circulatory arrest (CA, N=22) and subsequent resuscitation. Asphyxia in anesthetized rats was induced by rocuronium bromide injection, followed by recording of electrocardiogram (ECG), parameters of invasive blood pressure (BP) measurement and laser Doppler fluxmetry (LDF) to assess skin perfusion. CA episode was maintained for 2 min, followed by a series of resuscitation measures and intensive therapy for 2 h. Circulatory parameters (ECG, BP, LDF), gas composition and arterial blood acid-base state (ABS) dynamics were evaluated.Results. Monitored parameters were comparable in both groups at baseline after stabilization period. After exclusion criteria were applied 11 animals from SP group and 18 — from CA were included in the analysis. Tachycardia (heart rate, beats/min–1, SP vs CA) was documented in the CA group: 218 [205; 236] vs 286 [272; 305], P⩽0.0001), as well as recovery of skin perfusion to subnormal parameters in the first minutes after successful resuscitation. At minute 10 in the post-resuscitation period worsening of skin perfusion (M, perfusion units, SP vs CA): 14.7 [12.1; 16.5] vs 10.1 [7.0; 12.5], P=0.0014), and decompensated mixed acidosis (pH, SP vs CA): 7.42 [7.40; 7.43] vs 7.20 [7.13; 7.23], P⩽0.0001) were documented in the CA group, however BP values were comparable (BP, mmHg, SP vs CA): 60 [58; 72] vs 67 [62; 82], P=0.482). At minute 120 post-resuscitation and at the end of intensive care period, both groups demonstrated similar values of the monitored parameters. Three out of 18 animals in the CA group died after resuscitation.Conclusion. Electromechanical dissociation underlies CA in rats subjected to asphyxia. The use of LDF to assess peripheral blood flow makes it possible to standardize the severity of ischemic reperfusion injuries and improve reproducibility of the model. Series of resuscitation measures in experimental setting is justified from a bioethical point of view, and makes it possible to improve repeatability of preclinical research results in clinical practice.

American Association for the Surgery of Trauma/American College of Surgeons-Committee on Trauma Clinical Consensus-Driven Protocol for glucose management in the post-resuscitation intensive care unit adult trauma patient.

American Association for the Surgery of Trauma/American College of Surgeons-Committee on Trauma Clinical Consensus-Driven Protocol for glucose management in the post-resuscitation intensive care unit adult trauma patient.

Influence of blood-pressure and oxygen levels on the prognostic value of quantitative pupillometry for comatose cardiac arrest patients - a BOX-trial substudy

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Foundation Background Quantitative pupillometry has been implemented in resuscitation guidelines as part of multimodal prognostication in comatose out-of-hospital cardiac arrest (OHCA) patients. Post-resuscitation intensive care allows for different blood-pressure and oxygen targets, but evidence on the implication of these targets on prognostication is limited. Purpose To assess the impact of different blood-pressure and oxygen targets in resuscitated OHCA patients on the prognostic ability of the quantitatively assessed percentage reduction of pupillary size (qPLR, %) and the neurological pupil index (NPi, 0-5). Methods The BOX-trial is a multicenter, double-blind, randomized trial, comparing low (63 mm Hg) versus high (77 mm Hg) mean arterial blood-pressure targets and restrictive (9 to 10 kPa) versus liberal (13 to 14 kPa) partial pressure of arterial oxygen targets in comatose survivors of OHCA. In this predefined, prospective substudy, quantitative pupillometry measurements were obtained from consecutively enrolled patients at 0, 24, 48, 72, 96, and 120 hours after OHCA (t0-t120). The prognostic performance of qPLR and NPi for high and low blood-pressure groups, and liberal and restrictive oxygen target groups were illustrated through the area under the receiver operating characteristic (ROC) curves (AUC). The time point achieving the highest AUC was used for further analyses. AUCs were compared with DeLong’s test. Results The highest AUC for qPLR and NPi were achieved for measurements made 48 hours after OHCA. qPLR produced AUC at 0.79 [95%CI 0.73-0.85] and 0.81 [95%CI 0.75-0.86] for high and low blood-pressure groups, and 0.79 [95%CI 0.73-0.85] and 0.80 [95%CI 0.74-0.86] for liberal and restrictive oxygen target groups, respectively (Fig 1). For NPi AUC were 0.79 [95%CI 0.73-0.85] and 0.78 [95%CI 0.72-0.84] in high and low blood-pressure groups, and 0.77 [95%CI 0.71-0.83] and 0.80 [95%CI 0.75-0.86] in liberal and restrictive oxygen target groups, respectively (Fig 2). No significant difference between any groups, for either blood-pressure or oxygen targets, was found. Conclusion Prognostic value of quantitative pupillometry for predicting outcome in resuscitated OHCA patients was high and consistent across different blood-pressure and oxygen level targets.

Is jugular bulb oximetry monitoring associated with outcome in out of hospital cardiac arrest patients?

Cerebral protection against secondary hypoxic-ischemic brain injury is a key priority area in post-resuscitation intensive care management in survivors of cardiac arrest. Nevertheless, the current understanding of the incidence, diagnosis and its’ impact on neurological outcome remains undetermined. The aim of this study was to evaluate jugular bulb oximetry as a potential monitoring modality to detect the incidences of desaturation episodes during post-cardiac arrest intensive care management and to evaluate their subsequent impact on neurological outcome. We conducted a prospective, observational study in unconscious adult patients admitted to the intensive care unit who had successful resuscitation following out of hospital cardiac arrest of presumed cardiac causes. All the patients were treated as per European Resuscitation Council 2015 guidelines and they received jugular bulb catheter. Jugular bulb oximetry measurements were performed at six hourly intervals. The neurological outcomes were evaluated on 90th day after the cardiac arrest by cerebral performance categories scale. Forty patients met the eligibility criteria. Measurements of jugular venous oxygen saturation were performed for 438 times. Altogether, we found 2 incidences of jugular bulb oxygen saturation less than 50% (2/438; 0.46%), and 4 incidences when it was less than 55% (4/438; 0.91%). The study detected an association between SjVO2 and CO2 (r = 0.26), each 1 kPa increase in CO2 led to an increase in SjvO2 by 3.4% + / − 0.67 (p < 0.0001). There was no association between SjvO2 and PaO2 or SjvO2 and MAP. We observed a statistically significant higher mean SjvO2 (8.82% + / − 2.05, p < 0.0001) in unfavorable outcome group. The episodes of brain hypoxia detected by jugular bulb oxygen saturation were rare during post-resuscitation intensive care management in out of hospital cardiac arrest patients. Therefore, this modality of monitoring may not yield any additional information towards prevention of secondary hypoxic ischemic brain injury in post cardiac arrest survivors. Other factors contributing towards high jugular venous saturation needs to be considered.

Outcomes of paediatric out-of-hospital cardiac arrest according to hospital characteristic defined by the annual number of paediatric patients with invasive mechanical ventilation: A nationwide study in Japan

AimWe examined whether outcomes of paediatric out-of-hospital cardiac arrest (OHCA) are associated with a hospital characteristic defined by the annual number of invasive mechanical ventilation cases, suggesting hospitals’ experience in caring for severely ill paediatric patients. MethodWe analysed the Japanese Diagnosis Procedure Combination database from 2010 to 2017. We identified children (<18 years) with OHCA and post-resuscitation intensive care (defined as invasive mechanical ventilation and/or catecholamine infusion). Hospitals were divided into four groups by mean annual number of paediatric cases involving invasive mechanical ventilation. The primary outcome was in-hospital mortality, and the secondary outcome was unfavourable outcomes (death or medical care dependency at discharge). Multivariable logistic regression analyses were conducted to examine the relationship between hospitals’ experience and outcomes. ResultsWe included 2540 paediatric OHCA patients from 385 institutions. Overall in-hospital mortality was 62.4%, with rates of 69.6%, 61.3%, 61.8%, and 57.0% in hospitals with low (≤48 cases/year), low-intermediate (48–110), high-intermediate (110–164), and high (>164) experience levels (P < .001), respectively. Compared to hospitals with low experience, adjusted odds ratios (95% confidence interval) for hospitals with low-intermediate, high-intermediate, and high experience were as follows: primary outcome: 0.64 (0.40–1.01), 0.67 (0.42–1.05), and 0.46 (0.31–0.70), respectively; secondary outcome: 0.93 (0.55–1.57), 0.95 (0.63–1.43), and 0.67 (0.46–0.96), respectively. ConclusionJapanese hospitals with higher experience in caring for severely ill paediatric patients showed lower mortality for paediatric OHCA. This fact should be considered by the Emergency Medical Systems when deciding transport strategy.

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial

PurposeWe aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury.MethodsIn the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 23 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65–75 mmHg) vs. high-normal (80–100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest.ResultsWe recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2–34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6–30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes.ConclusionsTargeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.

Multidisciplinary Management of the Post-Cardiac Arrest Patient.

Cardiac arrest afflicts more than 300,000 persons annually in North America alone. Improving outcomes after cardiac arrest requires an integrated and multidisciplinary approach to postresuscitation intensive care and subsequent recovery. This article reviews components of injury within the post-cardiac arrest syndrome, the salient features of brain-oriented intensive care, best practices in neurologic prognostication, and a rational approach to emergency revascularization and hemodynamic support.

日本蘇生協議会蘇生ガイドライン ～小児の蘇生：心拍再開後集中治療

日本蘇生協議会蘇生ガイドライン ～小児の蘇生：心拍再開後集中治療

Anesthesia specific differences in a cardio-pulmonary resuscitation rat model; halothane versus sevoflurane

ObjectiveOur asphyxia cardiac arrest (ACA) rat model is well established. The original model was designed in the 1990th using halothane and nitrous oxide for pre-insult anesthesia. Because of its hepato-toxicity and its potential to induce severe liver failures, halothane is no longer used in clinical anesthesia for several years. In order to minimize the health risk for our laboratory staff as well as to keep the experimental settings of our model on a clinically oriented basis we decided to replace halothane by sevoflurane. In this study we intended to determine if the change of the narcotic gas regiment causes changes in the neurological damage and how far our model had to be adjusted. MethodsAdult rats were subjected to 5min of ACA followed by resuscitation. There were four treatment groups: ACA - halothane, ACA - sevoflurane and with halothane or sevoflurane sham operated animals. Vital and blood parameters were monitored during the 45min post-resuscitation intensive care phase. After a survival time of 7 days histological evaluation of the hippocampus was performed. ResultsWe observed that resuscitated rats anesthetized prior by sevoflurane (i) have had a lower heart rate and a higher MAP compared to halothane anesthetized animals; (ii) The neurological damaged were significantly reduced in the hippocampal CA1 region in sevoflurane treated rats. ConclusionUsing sevoflurane instead of halothane for anesthesia requires some physiological and experimental changes. However the model keeps its validity. Sevoflurane caused less pronounced neurodegeneration in the CA1 region of the hippocampus. This had to be considered in further resuscitation-studies containing sevoflurane as anesthetic.Institutional protocol number for animal studies: 42502-2-2–947 Uni MD.

Can we predict neurological outcome following out-of-hospital cardiac arrest (OHCA) and therapeutic hypothermia?

Can we predict neurological outcome following out-of-hospital cardiac arrest (OHCA) and therapeutic hypothermia?

Low-dose nitroglycerine improves outcome after cardiac arrest in rats

ObjectiveThe aim of this study was to evaluate the outcome of intravenously applied nitroglycerine (NTG, 1μgkg−1min−1 for 1h) after resuscitation from an asphyxia cardiac arrest (ACA) insult. We hypothesized that NTG infused for 1h after the return of spontaneous circulation (ROSC) would improve functional and neuro-morphological outcomes. MethodsAdult rats were subjected to 8min of ACA followed by resuscitation. There were three treatment groups: ACA, ACA+NTG and sham operated. Vital and blood parameters were monitored during the 1h post-resuscitation intensive care phase. After survival times of 3, 6, 12, 24, 72h and 7 days, the neurological deficit score (NDS) was measured. Histological evaluation of the hippocampus, cortex, the thalamic reticular nucleus and the caudate-putamen was performed 7 days post insult. ResultsWe found that NTG (i) induced significantly higher initial MAP peaks; (ii) resulted in a less-pronounced elevation of heart rates after ROSC with significantly faster normalization to baseline levels; and (iii) influenced glucose metabolism, temporarily elevating blood glucose to non-physiological levels. Even so, NTG (iv) improved the neurological outcome and (v) reduced neurodegeneration, mainly in the hippocampal CA1 region. A significant NTG-associated decrease in blood pressure did not occur. ConclusionThe effect of low-dosed NTG applied post-resuscitation appears to be neuroprotective, demonstrated by reduced hippocampal damage and a better NDS, even with temporarily elevated blood glucose to non-physiological levels. Thus, additional studies are needed to evaluate NTG-triggered mechanisms and optimized dosages before clinical translation should be considered.Animal study institutional protocol number: 42502-2-2-947-Uni-MD.

Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: A pilot study

ObjectivesTo investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA). Materials and methodsThis study was designed as a prospective observational study. Twenty-five patients, who received standard cardiopulmonary resuscitation and post-resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n=7, CPC 1 or 2) and Group P (n=18, CPC≥3). Their blood samples were taken at 6, 24, and 48h after ROSC. The patients, whose CSF was sampled at 48h, were also divided into either sub-Group G (n=6) or sub-Group P (n=8) at 6 months after ROSC. ResultsHMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4ng/ml, P=0.009; S100B, 2.68 vs. 84.2ng/ml, P=0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (σ=0.81, P=0.001). HMGB1 was elevated in serum at 6h and normalized within 48h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point. ConclusionsThe significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients.

Outcome after Admission to Intensive Care Unit Following Out-of-Hospital Cardiac Arrest: Comparison between Cardiac Etiology and Non-Cardiac Etiology

Background: To evaluate the post-resuscitation intensive care unit outcome of patients who initially survived out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively analyzed patients who were admitted to the ICU after OHCA in a tertiary hospital between January, 2005 and December, 2009. We compared the patients’ clinical data, the factors associated with admission and the prognosis of patients in cardiac and non-cardiac groups. Results: Sixty-four patients were included in this study. Thirty-four patients were in the cardiac group and thirty patients were in the non-cardiac group. The mean age was 57.3 ± 15.1 years of age in the cardiac group and 61.9 ± 15.7 years of age in the non-cardiac group (p = 0.235). The collapse-to-start of the CPR interval was 5.9 ± 3.8 min in the cardiac group and 6.0 ± 3.2 min in the non-cardiac group (p = 0.851). The complaint of chest pain occurred in 12 patients (35.3%) in the cardiac group and 1 patient (3.3%) in the non-cardiac group (p = 0.011). The time duration for making a decision for admission was 285.2 ± 202.2 min in the cardiac group and 327.7 ± 264.1 min in the non-cardiac group (p = 0.471). The regional wall motion abnormality and ejection fraction decrease were significant in the cardiac group (p = 0.002, 0.030). Grade 5 CPC was present in 8 patients (23.5%) in the cardiac group and 14 patients (46.7%) in the non-cardiac group. Conclusions: The key symptom that could initially differentiate the two groups was chest pain. The time duration for making an admission decision was long in both groups. The CPC score of the cardiac group was lower than that for the non-cardiac group.

Feasibility and efficacy of a new non-invasive surface cooling device in post-resuscitation intensive care medicine

There is sufficient evidence that therapeutic hypothermia after non-traumatic cardiac arrest improves neurological outcome and reduces mortality. Many different invasive and non-invasive cooling devices are currently available. Our purpose was to show the efficacy, safety and feasibility using a non-invasive cooling device to control patient temperature within a range of 33-37 degrees C. A convenience sample of patients who have been resuscitated successfully from cardiac arrest and were intended for mild hypothermia therapy according to the guidelines and inclusion criteria were studied in a prospective observational case series at an emergency department of a tertiary care university hospital. The Medivance Arctic Sun System provides a new, non-invasive approach to reach a target temperature of 33 degrees C quickly, to maintain the target temperature for 24h, and then to actively re-warm at 0.4 degrees C/h to normothermia. Cooling was applied using the Arctic Sun in 27 patients. Data are presented as median and the interquartile range (25, 75%). Median age was 58 (49.5, 70) years. Time from cooling start to target temperature was 137 (96, 168)min, cooling rate was 1.2 degrees C/h (0.8, 1.5), stability of target temperature during hypothermia maintenance phase was satisfactory at 33.0 degrees C (32.9, 33.1), and duration of re-warming was 428 (394, 452)min. Using the Arctic Sun System in post-resuscitation care medicine for cooling cardiac arrest survivors is feasible and has proven to be highly effective in lowering patients' temperature rapidly without inducing skin irritations.

Studies of the protein synthesis system in the brain cortex during global ischemia and reperfusion

Previous studies have demonstrated that brain protein synthesis declines after global ischemia and reperfusion. To investigate the role of the translation system in this phenomenon, we examined the ability of partially purified ribosomes, ribosome-bound mRNA and translation cofactors derived from the transiently ischemic cerebral cortex to synthesize protein in vitro. Samples were prepared from canines subjected to 20-min cardiac arrest and after 2 or 8 h of post-resuscitation intensive care. There was no significant decrease in the rate of in vitro protein synthesis as a consequence of either ischemia or reperfusion. Northern hybridization of ribosome-bound RNA revealed a discrete band of mRNA for brain-specific creatine kinase ( ck-bb) that was consistent in presence and intensity in all groups. However, mRNA for heat shock 70 protein ( hsp-70) was observed only during reperfusion and markedly increased between 2 and 8 h reperfusion. Thus, we conclude that (1) the transcription system is intact during reperfusion and hsp-70 mRNA is made and translocated to the ribosomes during reperfusion, (2) mRNA for ck-bb is not displaced from ribosomes by the appearance of hsp-70 during reperfusion and (3) isolated ribosomes maintain their ability to translate in vitro during the first 8 h of reperfusion after global brain ischemia. Therefore, the early reduction in protein synthesis observed in vivo during post-ischemic brain reperfusion is not due to an intrinsic dysfunction of the ribosomes.

The pathophysiology of cardiorespiratory arrest and principles of post-resuscitation intensive care.

Oxygen supply to the tissues is dependent on both cardiac output (which is determined by blood volume and myocardial function) and the oxygen tension of arterial blood (which reflects respiratory status). Abnormalities of these parameters may occur individually or together to progress ultimately to combined cardiorespiratory collapse. Life support measures are then required to restore the oxygen supply to vital organs, such as the brain, heart, kidneys and liver while attempts to restore normal cardiorespiratory status are made. Survival following cardiorespiratory arrest is enhanced if resuscitation is promptly instituted by skilled resuscitators, and a clear understanding of the mechanisms of cardiorespiratory collapse are essential to the efficient management of these patients.