Antti Kämäräinen

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial.

Background: Intravenous infusion of ice‐cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients.

Induction of therapeutic hypothermia during prehospital CPR using ice-cold intravenous fluid ☆

AIM OF THE STUDY Primarily, to investigate induction of therapeutic hypothermia during prehospital cardiopulmonary resuscitation (CPR) using ice-cold intravenous fluids. Effects on return of spontaneous circulation (ROSC), rate of rearrest, temperature and haemodynamics were assessed. Additionally, the outcome was followed until discharge from hospital. MATERIALS AND METHODS Seventeen adult prehospital patients without obvious external causes for cardiac arrest were included. During CPR and after ROSC, paramedics infused +4 degrees C Ringers acetate aiming at a target temperature of 33 degrees C. RESULTS ROSC was achieved in 13 patients, 11 of whom were admitted to hospital. Their mean initial nasopharyngeal temperature was 35.17+/-0.57 degrees C (95% CI), and their temperature on hospital admission was 33.83+/-0.77 degrees C (-1.34 degrees C, p<0.001). The mean infused volume of cold fluid was 1571+/-517 ml. The rate of rearrest after ROSC was not increased compared to previous reports. Hypotension was observed in five patients. Of the 17 patients, 1 survived to hospital discharge. CONCLUSION Induction of therapeutic hypothermia during prehospital CPR and after ROSC using ice-cold Ringers solution effectively decreased nasopharyngeal temperature. The treatment was easily carried out and well tolerated.

Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest.

To investigate the incidence of iatrogenic dyscarbia in survivors of out-of-hospital cardiac arrest treated with induced mild hypothermia.We performed a retrospective cohort study of the ventilatory management based on blood gas analyses of patients resuscitated from prehospital cardiac arrest. In the pilot phase, we assessed the ventilatory management in the patients treated in one university hospital during a 4-year study period. Subsequently, a more recent (1-year) retrospective cohort of resuscitated patients from all five Finnish university hospitals concerning the first 48h after hospital admission was analyzed. Core temperatures and temperature corrected (or non-corrected) blood gas analysis results with focus on carbon dioxide tension were analyzed. In addition, a survey was performed to investigate the ventilatory strategies in all Finnish hospitals providing mild hypothermia for cardiac arrest victims.The pilot cohort suggested a high incidence of hypo- or hyper-carbia during hypothermia treatment. In the multicenter patient population of 122 patients contributing a total of 1627 measurements, the PaCO(2) distribution was as follows: less than 4 kPa in 148 samples out of 1627 (9%), 4-4.6 kPa in 404 (25%), 4.7-6 kPa in 887 (55%) and more than 6 kPa in 188 samples (12%). There was a significant difference in the incidence of hypercarbia between the hospitals (p<0.05).We conclude that normocarbia was achieved/maintained only in approximately 55% of the samples. The incidence of hypo- or hyper-carbia (dyscarbia) was high (45%). This may predispose for serious derangements in the cerebral perfusion of the resuscitated patient. These results call for vigilance in adjustment of the ventilatory management to meet the needs of the patients treated with mild hypothermia.

Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest

AIM The quality of cardiopulmonary resuscitation (CPR) is associated with the rate of return of spontaneous circulation (ROSC) during human cardiac arrest. Current advances in defibrillator technology enable measurement of CPR quality during resuscitation, but it is not known whether this is directly reflected in cerebral oxygenation. In this descriptive study we aimed to evaluate whether the quality of feedback-monitored CPR during in-hospital cardiac arrest is reflected in near infrared frontal cerebral spectroscopy (NIRS). METHODS Nine patients suffering an in-hospital cardiac arrest in a university hospital were included. All patients underwent quality-controlled CPR performed by a dedicated medical emergency team using a Philips HeartStart MRx defibrillator (Philips, Eindhoven, Netherlands) with a CPR quality (Q-CPR, Laerdal Medical, Stavanger, Norway) analysis feature. Simultaneously, bilateral frontal cerebral oximetry was measured using INVOS 5100c (Somanetics, Troy, MI, USA) NIRS. RESULTS During quality controlled resuscitation, regional cerebral oxygenation (rSO(2)) as measured with NIRS was low but it improved during CPR (p=0.043) and 8 min after ROSC (p=0.022). After the onset of NIRS recording, there were four episodes exceeding 30s, during which the quality of CPR was substandard. When CPR technique was corrected and maintained for 2 min, a minor non-significant increase in rSO(2) was observed in two cases. CONCLUSIONS High quality CPR was not significantly reflected in cerebral oxygenation as quantified using NIRS. Even after ROSC and subsequent significant increase in cerebral oxygenation, rSO(2) readings were below previously suggested threshold of cerebral ischaemia. Improving CPR technique after an episode of low quality CPR did not significantly increase rSO(2).

Therapeutic hypothermia after cardiac arrest – cerebral perfusion and metabolism during upper and lower threshold normocapnia

BACKGROUND During cardiac arrest and after successful resuscitation a continuum of ischaemia-reperfusion injury develops. Mild hypothermia exerts protective effects in the postresuscitation phase but also alters CO₂ production and solubility, which may lead to deleterious effects if overlooked when adjusting the ventilation of the resuscitated patient. Using a multimodality approach, the effects of different carbaemic states on cerebral perfusion and metabolism were evaluated during therapeutic hypothermia. METHODS Eight comatose survivors of prehospital cardiac arrest were cooled to 33°C for 24 h and underwent a 60 min phase of interventional lower threshold normocapnia according to temperature non-corrected pCO₂ (4.2 kPa) and higher threshold normocapnia according to corrected pCO₂ (6.0 kPa) in a random order. Prior to, during and after each phase, cerebral perfusion and metabolites via a microdialysis catheter were measured. RESULTS During upper-threshold pCO₂, an increase in middle cerebral artery mean flow velocity (MFV) and jugular bulb oxygen saturation (jSvO₂) were observed with a concomitant decrease in cerebral lactate concentration. Lower threshold normocapnia was associated with a decrease in MFV in most patients. In all patients jSvO₂ decreased but no change in cerebral lactate was observed. In seven patients jSvO₂ decreased below 55%. These changes were not reflected to intracranial pressure or cerebral oximetry. CONCLUSIONS During induced hypothermia, lower threshold normocapnia was associated with decreased cerebral perfusion/oxygenation but not reflected to interstitial metabolites. Upper threshold pCO₂ increased cerebral perfusion and reduced cerebral lactate. Vigilance over the ventilatory and CO₂ analysis regimen is mandatory during mild hypothermia.

Conduct of emergency research in patients unable to give consent—Experiences and perceptions of patients, their consent providing next of kin, and treating physicians following a prehospital resuscitation trial☆

OBJECTIVE According to a directive of the European Parliament, informed consent is required to conduct a clinical trial also in emergencies when the patient is unable to provide consent. In these cases surrogate consent can be obtained from the patients next of kin. There are no reports describing how patients and their next of kin perceive this policy. The perceptions of patients and their spouses involved in an emergency trial conducted under surrogate consent were surveyed. METHODS A survey was sent to survivors of prehospital cardiac arrest, to consent providers regardless of patient outcome, and to physicians who had recruited the patients. RESULTS 11 (92%) patients, 17 (68%) consent providers, and all physicians returned the survey. All held a positive attitude towards emergency research and were willing to participate without own consent in a trial approved by an institutional review board (IRB). Opinions among responding groups were similar albeit a significant difference regarding the perceived capability of the consent provider to decide upon patients enrolment. Spouses felt able to provide consent, but physicians were sceptical of this. Patients and their spouses would have appreciated additional information regarding the index trial after the acute phase. CONCLUSIONS Emergency research was perceived positively by cardiac arrest victims and their spouses previously involved in a resuscitation trial. Possible own participation in an emergency trial without personal consent was considered acceptable. Patients and their spouses would prefer additional research information after enrolment.

Hypothermic preconditioning of donor organs prior to harvesting and ischaemia using ice-cold intravenous fluids

To promote organ transplantation and viability, hypothermia has been applied as a protective agent for decades. Current management of organ preservation includes hypothermia as a component of static storage. In rare cases, hypothermic perfusion is initiated in the donor organs prior to harvesting but this requires invasive perfusion techniques. Therefore, hypothermic organ protection is currently achieved only after organ retrieval and onset of ischaemic injury cascades. The relevant mechanisms of cellular and organ damage involve ischaemia-reperfusion injury and apoptosis. In this hypothesis, we propose the possibility of inducing hypothermic protective effects prior to organ harvesting using infusion of ice-cold (+4 degrees C) intravenous fluid in the organ donor. This method of cooling to mild hypothermia (32-34 degrees C) has been found feasible in e.g. cardiac arrest victims and already during the ischaemic insult. We hypothesize that cooling with ice-cold fluid preceding organ harvesting would downregulate organ metabolism and oxygen consumption resulting in improved tolerance to ischaemia. Furthermore, according to existing evidence, mild hypothermia possesses anti-apoptotic effects and suppresses reperfusion associated inflammatory response. Finally, diabetes insipidus is often observed in the brain dead donor. Subsequent hypovolemia is conveniently treated with additional infusion of cold intravenous fluid. We offer this hypothesis as a simple method of improving donor organ viability via improved tolerance to ischaemia and reperfusion injury. This method of hypothermic preconditioning seems safe, inexpensive and easily applicable in virtually every institution treating organ donors. The feasibility and effects of this hypothesis could be further evaluated in comparison to current treatment protocols in laboratory settings including evaluation of organ preservation.

Statins for post resuscitation syndrome.

After sudden cardiac arrest, successful resuscitation and return of spontaneous circulation, a multi-faceted ischaemia/reperfusion related disorder develops. This condition now known as post resuscitation syndrome is characterised by marked increases in the inflammatory response and changes in coagulation profile and vascular reactivity. Additionally, the production of reactive oxygen species and activation of cytotoxic cascades of metabolism add to these injury mechanisms resulting in multiorgan perfusion deficits and dysfunction. Especially in the cerebrum these injuries may be the cause of significant morbidity and mortality. Recent evidence has shown that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert numerous beneficial effects in cardiovascular diseases irrespective of the lipid status. Remarkably, these pleiotropic effects seem to extended beyond cardiovascular diseases such as immunomodulative and antioxidative properties. We hypothesised that administration of statins early in the post resuscitation phase would prove beneficial in the resuscitated patient via several pleiotropic effects. These include inhibition of excessive coagulation and inflammatory response, suppression of oxygen radical production and improved vascular reactivity. The discussed effects are mediated via multiple pathways activated in the cardiac arrest victim, to which statins have been shown to have a beneficial modulating effect in experimental settings and non-cardiac arrest patients. To test this hypothesis in clinical practice, a randomized, controlled trial with sufficient power and standardised post resuscitation treatment would be necessary. The generally good tolerance of statin therapy with minimal adverse effects would support this experiment, although a parenteral form of the drug to ensure adequate dosage might be a prerequisite.

Pulseless electrical activity and successful out-of-hospital resuscitation – long-term survival and quality of life: an observational cohort study

BackgroundThe aim of the study was to evaluate the long-term outcome of patients successfully resuscitated from pre-hospital cardiac arrest with initial pulseless electrical activity (PEA), because the long-term outcome of these patients is unknown. Survival, neurological status one year after cardiac arrest and self-perceived quality of life after five years were assessed.MethodsThis retrospective study included adult patients resuscitated from PEA between August 2001 and March 2003 in three urban areas in southern Finland. A validated questionnaire was sent to patients while neurological status according to the Cerebral Performance Category (CPC) -classification was assessed based on medical database notes recorded during follow-up evaluations.ResultsOut of 99 included patients in whom resuscitation was attempted, 41 (41%) were successfully resuscitated and admitted to hospital. Ten (10%) patients were discharged from hospital. Seven were alive after one year and six after five years following cardiac arrest. Five of the seven patients alive one year after resuscitation presented with the same functional level as prior to cardiac arrest.ConclusionsPatients with initial PEA have been considered to have poor prognosis, but in our material, half of those who survived to hospital discharge were still alive after 5 years. Their self-assessed quality of life seems to be good with only mild to moderate impairments in activities of daily life.

Assessment of futility in out‐of‐hospital cardiac arrest

Our aim was to evaluate the impact of futile resuscitation attempts to the outcome calculations of attempted resuscitation in out‐of‐hospital cardiac arrest (OHCA). Defined as partial resuscitations, we focused on a subgroup of patients in whom cardiopulmonary resuscitation (CPR) was initiated, but further efforts were soon abandoned due to evidence of futility.