Clinical paperHypertonic saline during CPR: Feasibility and safety of a new protocol of fluid management during resuscitation☆
Introduction
If defibrillation fails or if the initial ECG rhythm is not ventricular fibrillation (VF) resuscitation success after cardiac arrest (CA) depends crucially on reperfusion of the heart. Myocardial reperfusion during cardiopulmonary resuscitation (CPR) can be improved by an increase in systemic vascular resistance, i.e. by the application of the vasopressors like adrenaline (epinephrine) or vasopressin.1, 2, 3 However, this concept does not cover the fact that other pathophysiological changes such as haemoconcentration, endothelial cell swelling and rolling, and adhesion of leucocytes also compromise myocardial and cerebral reperfusion. Several experimental studies after CA and CPR demonstrated haemoconcentration due to capillary leakage and plasma loss of up to 20 ml/kg.4, 5, 6 One therapeutic option to compensate this plasma loss could be the infusion of a large volume of an isotonic solution. This approach, however, decreases cerebral and myocardial perfusion pressure during CPR.7, 8, 9
A well-known measure to increase blood volume and to improve haemodynamics and nutritive organ blood flow in haemorrhagic shock and brain trauma is to use a small volume of a hypertonic solution (“small volume resuscitation”).10, 11, 12, 13, 14, 15 In the last decade the use of hypertonic solutions during CPR was investigated systematically in several experimental studies.16, 17, 18, 19, 20, 21 The rationale to test this therapeutic option during CPR were the known effects of hypertonic solutions from hemorrhagic shock models, i.e. an increase of the intravascular volume, and a decrease of the ischaemic endothelial cell swelling and leukocyte activation. In experimental CA/CPR models the use of hypertonic saline significantly increased myocardial blood flow (MBF), myocardial perfusion pressure (MPP), and cardiac index (CI) during CPR.16, 20 In addition, microcirculatory reperfusion of the brain was improved and cerebral blood flow (CBF) during CPR was sustained or even improved in HHS treated animals.17, 18, 19, 20 In these experimental studies infusion of hypertonic solution significantly increased resuscitation success and survival rate.16, 17, 20 Furthermore, Krieter et al. found that hypertonic saline application after resuscitation from CA reduced astroglial S-100β protein release, which might indicate a possible reduction in neuronal injury after CPR.22
In the treatment of haemorrhagic shock a dose of 4 ml/kg bodyweight is recommended. After CA similar effects on myocardial reperfusion and success rate were found after infusion of 2 or 4 ml/kg hypertonic saline.20 A maximum plasma loss of 16 ml/kg was found by Lin and a solution of 7.2% NaCl showed a plasma expansion capacity of about eight-fold,10, 23 a dose of 2 ml/kg bodyweight was used in our preclinical pilot study.
In human CA, however, comorbidity and haemodynamics during external chest compressions and after CPR may be different compared to animal experiments. We, therefore, studied the feasibility and safety of an intravenous infusion of hypertonic saline/hydroxy ethyl starch (HHS) during preclinical CPR after out-of-hospital CA.
Section snippets
Materials and methods
The study was conducted by the Department of Anaesthesiology and Intensive Care Medicine of the University Bonn, Germany. It was in accordance with the declaration of Helsinki and in accordance with all current German regulations and standards for investigations upon human subjects after approval of the local ethical committee. Information and consent of the patients or relatives in advance of the study was not practicable, but the patients’ families and surviving patients were informed
Patients
Starting in May 2001, patients who experienced CA were screened for inclusion. Included were all patients with out-of-hospital cardiac arrest of non-traumatic origin, with the need of adrenaline during CPR, an age ≥18 years, duration of cardiac arrest ≤15 min and body weight ≤125 kg. Excluded were patients with ROSC before starting infusion of the study drug, known malignancy, pregnancy, and renal or heart failure (NYHA IV). Duration of CA was defined as the interval from the moment of collapse
General management
The acute medical care, including basic and advanced life support was carried out by the EMS physicians and paramedics in accordance with the German- and ILCOR-guidelines 2000.2, 24 When CA was confirmed an ECG was recorded and CPR was started. After cannulation of an external jugular vein the patients randomly received 2 ml/kg/10 min of either hypertonic saline with hydroxy ethyl starch (HHS; 7.2% NaCl with 6% hydroxy ethyl starch 200,000/0.5 [HES]) or HES in a blinded manner. After successful
Blood analysis
Before and 10 min after infusion of the study solution 5 ml of venous blood was taken to measure haemoglobin, pO2, pH, HCO3, BE, plasma sodium and potassium concentrations. The blood was cooled within a transportable cool box and analysed later in the admitting hospital. Directly after admission to hospital 1 ml arterial blood was taken to measure blood gases, haemoglobin, glucose, plasma sodium and potassium concentrations.
Data evaluation
Time of emergency call reception and ambulance stop on arrival at the scene was documented precisely by the fire departments dispatch centre. The intervals between ambulance stop at the scene and patient contact and all important facts during CPR were taken from the defibrillator protocols. All other preclinical data concerning the patient were obtained by evaluating a standard protocol and interviewing the emergency physician after CPR. In case of a successful resuscitation one doctoral
Statistical analysis
This clinical investigation was designed as a pilot study, because to date there is no clinical experience published investigating the effects of hypertonic saline solutions during resuscitation from cardiac arrest. This first data will help to design an enlarged study powered to a primary endpoint of survival to hospital admission. All numerical data are expressed as means ± standard deviation (S.D.). Differences between groups and time points were analysed for significance by the χ2-test,
Patients
Within an observation period of 11 months 66 patients with out-of-hospital CA of non-traumatic origin were included into the study protocol. Four patients did not match the study criteria: in three cases duration of cardiac arrest was >15 min and one patient developed ROSC without adrenaline. The median age of the patients was equal in both groups (HHS 64 years, HES 65 years). In the HHS group 76% of patients were male and 24% female, in the HES group 70% of patients were male and 30% female (p =
Discussion
To the best of our knowledge, this is the first human study investigating the infusion of hypertonic saline solution after out-of-hospital CA to test the safety and the feasibility of this new protocol of fluid management during CPR. We found that the infusion of 2 ml/kg/10 min HHS (7.2% NaCl with 6% hydroxy ethyl starch 200,000/0.5) during CPR is safe and feasible. It is a simple and practicable method to improve reperfusion of the heart and the brain that can be applied within the usual
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Hypertonic saline infusion during resuscitation from out-of-hospital cardiac arrest: A matched-pair study from the German Resuscitation Registry
2014, ResuscitationCitation Excerpt :Such studies have also shown that treatment with HS after CA improves microcirculatory reperfusion of the brain and heart22,25–28 and short-term survival,26–28 reduces protein-S100 and troponin release after CPR,29 and improves neurological recovery after forebrain ischaemia.30 Based on these findings we undertook a randomized clinical trial (RCT) using 2 ml kg−1 body weight HS/hydroxyethyl starch (HES) or HES alone during CPR after OHCA.31,32 In 200 patients, we failed to demonstrate that administration of HS improves admission to hospital or hospital discharge rate.
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2013, Veterinary Anaesthesia: Eleventh EditionSex differences in cardiac injury after severe haemorrhage and ventricular fibrillation in pigs
2010, ResuscitationCitation Excerpt :In the current study, therefore, we seek to evaluate these gender differences using the same model of exsanguination CA. We chose to administer hypertonic saline and dextran solution (HSD) for volume resuscitation during cardiopulmonary resuscitation (CPR), based on the evidence that hypertonic saline improves myocardial and cerebral reperfusion.5,6 The addition of dextran provides enhanced volume expansion capacity and prolonged intravascular persistence.7
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2006.05.019.