Randomised study of hypertonic saline infusion during resuscitation from out-of-hospital cardiac arrest.

AIM OF THE STUDY: Animal models of hypertonic saline infusion during cardiopulmonary resuscitation (CPR) improve survival, as well as myocardial and cerebral perfusion during CPR. We studied the effect of hypertonic saline infusion during CPR (Guidelines 2000) on survival to hospital admission and hospital discharge, and neurological outcome on hospital discharge. METHODS: The study was performed by the EMS of Bonn, Germany, with ethical committee approval. Study inclusion criteria were non-traumatic out-of-hospital cardiac arrest, aged 18-80 years, and given of adrenaline (epinephrine) during CPR. Patients were randomly infused 2 mlkg(-1) HHS (7.2% NaCl with 6% hydroxyethyl starch 200,000/0.5 [HES]) or HES over 10 min. RESULTS: 203 patients were randomised between May 2001 and June 2004. After HHS infusion, plasma sodium concentration increased significantly to 162±36 mmoll(-1) at 10 min after infusion and decreased to near normal (144±6 mmoll(-1)) at hospital admission. Survival to hospital admission and hospital discharge was similar in both groups (50/100 HHS vs. 49/103 HES for hospital admission, 23/100 HHS vs. 22/103 HES for hospital discharge). There was a small improvement in neurological outcome in survivors on discharge (cerebral performance category 1 or 2) in the HHS group compared to the HES group (13/100 HHS vs. 5/100 HES, p<0.05, odds-ratio 2.9, 95% confidence interval 1.004-8.5). CONCLUSION: Hypertonic saline infusion during CPR using Guidelines 2000 did not improve survival to hospital admission or hospital discharge. There was a small improvement with hypertonic saline in the secondary endpoint of neurological outcome on discharge in survivors. Further adequately powered studies using current guidelines are needed.

Coagulation management in multiple trauma: a systematic review.

PURPOSE: The management of trauma patients suffering from active bleeding has improved with a better understanding of trauma-induced coagulopathy. The aim of this manuscript is to give recommendations for coagulation management. METHODS: A systematic literature search in the PubMed database was performed for articles published between January 2000 and August 2009. A total of 230 articles were included in the present systematic review. CONCLUSIONS: The "coagulopathy of trauma" is a discrete disease which has a decisive influence on survival. Diagnosis and therapy of deranged coagulation should start immediately after admission to the emergency department. A specific protocol for massive transfusion should be introduced and continued. Loss of body temperature should be prevented and treated. Acidaemia should be prevented and treated by appropriate shock therapy. If massive transfusion is performed using fresh frozen plasma (FFP), a ratio of FFP to pRBC (packed red blood cells) of 1:2-1:1 should be achieved. Fibrinogen should be substituted at levels of <1.5 g/L. For patients suffering from active bleeding, permissive hypotension (i.e. mean arterial pressure ~65 mmHg) may be aimed for until surgical cessation of bleeding. This option is contraindicated in injuries of the central nervous system and in patients with coronary heart disease, or with known hypertension. Thrombelastography or -metry may be performed to guide coagulation diagnosis and substitution. Hypocalcaemia <0.9 mmol/L should be avoided and may be treated. For actively bleeding patients, pRBC may be given at haemoglobin <10 g/L (6.2 mmol/L) and haematocrit may be targeted at 30%.

Effects of hydroxyethyl starch, gelatin and dextran on endothelium-derived relaxation in porcine coronary arteries.

BACKGROUND: In a pilot study we could show that hydroxyethyl starch (HES) induced a significant reduction of endothelium-dependent relaxation (EDR) and the endothelium-derived hyperpolarizing factor (EDHF). In this follow-up study we investigated whether this effect of HES was dose-dependent and whether it could be replicated with other colloids like dextran (DX) and gelatin (GL). METHODS: Rings of fresh porcine coronary arteries were consecutively tested with or without HES, DX or GL (5, 10, or 20 mg/ml). Indomethacin was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2α was used for contraction and bradykinin (BK, 10⁻¹° to 10⁻5 M) for inducing EDR. After blocking nitric oxide (NO) by N-nitro-L-arginine (L-NNA), the experiments were repeated to assess the EDHF-mediated relaxation response to BK. RESULTS: HES induced a reduction in EDR for the BK concentrations of 10⁻8 and 10⁻7 M (n = 10; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10⁻6 and 10⁻5 M (p < 0.05). GL showed a reduction in EDR with or without NO blockage with L-NNA especially for the BK concentrations of 10⁻6 and 10⁻5 M (n = 14; p < 0.05). DX induced a significant reduction in EDR for the BK concentrations of 10⁻7 and 10⁻6 M (n = 12; p < 0.05). After NO blockage with L-NNA, the relaxation response was reduced especially for the BK concentrations of 10⁻6 and 10⁻5 M (p < 0.05). CONCLUSION: For clinically relevant concentrations of HES, DX and GL a significant reduction in both NO-induced and NO-/prostacyclin-independent EDR can be found in epicardial coronary arteries of the pig.

Chronic pain and disability after pelvic and acetabular fractures--assessment with the Mainz Pain Staging System.

BACKGROUND: Chronic posttraumatic pelvic pain (PPP) after pelvic ring fractures impacts negatively on quality of life issues. This study aimed to more clearly identify and quantify the problem. METHODS: For this cross-sectional study, patients were examined 52 (median) months after pelvic fractures. The following parameters were measured: pain chronicity (Mainz Pain Staging System [MPSS]), pain intensity (Numeric Rating Scale, 0-10), pelvic fracture outcome scores (Majeed, Pohlemann, and Bürk), pain severity (Chronic Pain Grading Questionnaire), pain-related interference with activities of daily living (Chronic Pain Grading Questionnaire), low back pain-related disability (Oswestry score), neuropathic pain (painDETECT), physical functioning (Short Form-12), and medical comorbidities (Weighted Illness Check List-20). Psychological distress was evaluated for anxiety and depression (Hospital Anxiety and Depression Scale) and mental quality of life (Short Form-12). RESULTS: Sixty-nine patients had a total of 49 pelvic and 41 acetabular fractures; 70% underwent osteosynthesis. The prevalence of PPP was 64%. Prevalence weighted with the dysfunctional pain chronicity stages MPSS II and III was 48%. Patients with pelvic fracture types (AO classification) A, B, and C had PPP prevalences of 38%, 67%, and 90%, respectively. Pain chronicity stages (MPSS) were moderately to strongly correlated with pelvic pain intensity (r = 0.57), the three pelvic fracture outcome scores (r = -0.78 to -0.90), pain-related interference (r = 0.72), Oswestry score (r = 0.68), nerve injury and neuropathic pain (r = 0.52), reduced physical (r = -0.72) and mental functioning (r = -0.58), trauma-related comorbidity (r = 0.53), anxiety (r = 0.51), and depression (r = 0.67). CONCLUSION: This study demonstrated that the intensity and prevalence of PPP are high even some 4 years after injury. The validated instruments MPSS (measuring pain chronicity) and Oswestry disability score proved to be appropriate for classifying outcome after pelvic ring fractures.

Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma.

BACKGROUND: Beside the often discussed topics of consumption and dilution coagulopathy, additional perioperative impairments of coagulation are caused by acidosis, hypocalcemia, anemia, hypothermia, and combinations. METHODS: Reviewing current literature, cutoff values of these parameters become obvious at which therapy should commence. RESULTS: A notable impairment of hemostasis arises at a pH < or = 7.1. Similar effects are caused by a BE of -12.5 or less. Thus, in case of severe bleeding, buffering toward physiologic pH values is recommended, especially with massive transfusions of older RBCCs displaying exhausted red blood cell buffer systems. It completes the optimization of the volume homeostasis to ensure an adequate tissue perfusion. Combining beneficial cardiovascular and coagulation effects, the level for ionized calcium concentration should be held > or = 0.9 mmol/L. From the hemostatic point of view, the optimal Hct is higher than the one required for oxygenation. Even without a "classical" transfusion trigger, the therapy of acute, persistent bleeding should aim at reaching an Hct > or = 30%. A core temperature of < or = 34 degrees C causes a decisive impairment of hemostasis. A controlled hypotensive fluid resuscitation should aim at reaching a mean arterial pressure of > or = 65 mm Hg (possibly higher for cerebral trauma). Prevention and later aggressive therapy of hypothermia by exclusive infusion of warmed fluids and the use of warming devices are prerequisites for the cure of traumatic coagulopathy. Combined appearance of single preconditions cause additive impairments of the coagulation system. CONCLUSIONS: The prevention and timely correction, especially of the combination acidosis plus hypothermia, is crucial for the treatment of hemorrhagic coagulopathy.

Hydroxyethyl starch inhibits endothelium-derived relaxation in porcine coronary arteries.

OBJECTIVE: Hydroxyethyl starch (HES) solutions are widely used for fluid resuscitation. We studied the effects of HES on endothelium-dependent relaxation (EDR), especially on the endothelium-derived hyperpolarizing factor (EDHF). METHODS: Four-millimeter-long rings of fresh porcine coronary arteries from the local slaughterhouse were consecutively tested with or without HES (6 mg/ml). Indomethacin (10 micromol/l) was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2alpha (10 micromol/l) was used for contraction and bradykinin (10(-10) to 10(-5) mol/l) for inducing EDR, which was calculated in percentage of the precontraction. After blocking all nitric oxide formation by N-nitro-L-arginine (300 micromol/l), the experiments were repeated to assess the EDHF-mediated relaxation response to bradykinin. RESULTS: HES 6 mg/ml induced a significant (p < 0.01) reduction in EDR (n = 8). After incubation with HES and nitric oxide blockage with N-nitro-L-arginine, the relaxation response was reduced especially for the bradykinin concentrations of 10(-6) mol/l (p < 0.05) and 10(-5) mol/l (p < 0.01). CONCLUSION: For the clinically relevant concentration of 6 mg/ml HES, a significant reduction in EDR and the EDHF can be found in epicardial coronary arteries of the pig.

Subannular perforation after long-lasting aortic valve replacement mimicking mitral insufficiency.

We report a rare case of a patient diagnosed with mitral insufficiency grade III 12 years after mechanical aortic valve replacement. Transesophageal echocardiography described an eccentric mitral regurgitation-type systolic jet with color flow evidence of communication between left ventricle and atrium. Surgical intervention showed a circular defect in the mitral-aortic intervalvular fibrosa area, after removal of the mechanical valve, located beneath the noncoronary sinus causing the echocardiography-detected mitral insufficiency. A pericardial patch was trimmed to the appropriate size, and the defect was closed. The aortic valve was replaced by a stented pericardial bioprosthesis.

Out-of-hospital cardiopulmonary resuscitation with the AutoPulse system: a prospective observational study with a new load-distributing band chest compression device.

OBJECTIVE: To evaluate the effectiveness, the safety, and the practicability of the new automated load-distributing band resuscitation device AutoPulse in out-of-hospital cardiac arrest in the midsized urban emergency service of Bonn city. STUDY DESIGN: Prospective, observational study. METHODS: Measurements of effectiveness were the proportion of patients with a return of spontaneous circulation (ROSC) and end-tidal carbon-dioxide (etCO(2)) values during cardiopulmonary resuscitation (CPR). The indications of safety was the proportion of injuries caused by the device, and practicability was assessed by the measurement of the time taken to setup the AutoPulse. RESULTS: Forty-six patients were resuscitated with the device from September 2004 to May 2005. In 25 patients (54.3%) ROSC was achieved, 18 patients (39.1%) were admitted to intensive care unit (ICU), and 10 patients (21.8%) were discharged from ICU. End-tidal capnography showed significantly higher etCO(2) values in patients with ROSC than in patients without ROSC. The mean time to setup the AutoPulse was 4.7+/-5.9 min, but activation of the device after arrival at the scene in 2 min or less was possible in 67.4%. No injuries were detected after use of the AutoPulse-CPR. CONCLUSION: The AutoPulse system is an effective and safe mechanical CPR device useful in out-of-hospital cardiac arrest CPR. Automated CPR devices may play an increasingly important role in CPR in the future because they assure continuous chest compressions of a constant quality.

Hypertonic saline during CPR: Feasibility and safety of a new protocol of fluid management during resuscitation.

BACKGROUND AND PURPOSE: In experimental studies infusion of hypertonic saline during cardiopulmonary resuscitation (CPR) increased resuscitation success rate and improved myocardial and cerebral reperfusion during CPR. We tested the feasibility and the safety of this new therapeutic measure in a randomised, preclinical pilot study. METHODS: The study was performed in the EMS system of Bonn after approval of the local ethical committee. Study inclusion criteria were out-of-hospital cardiac arrest (CA) of non-traumatic origin, age > or =18 years, application of adrenaline (epinephrine) during CPR, duration of CA < or = 15 min, and estimated body weight < or = 125 kg. Patients randomly received 2 ml/kg/10 min HHS (7.2% NaCl with 6% hydroxy ethyl starch 200,000/0.5 [HES]) or HES alone. Haemoglobin, blood gases, plasma sodium and potassium concentrations were measured before and 10 min after infusion, and after admission to hospital. Feasibility and safety of the new fluid management was evaluated by looking for side effects and determination of resuscitation success and admission rates. RESULTS: Sixty-six patients were included. After infusion of HHS, plasma sodium concentration increased to 168+/-29 mmol/l at 10 min after application but already decreased to near normal (147+/-5.5 mmol/l) at admission to hospital. Patients receiving HHS showed a trend to higher resuscitation success and hospital admission rates (ROSC: HHS 66.7%, HES 51.5%, p = 0.21; admission: HHS 57.6%, HES 39.4%, p = 0.14). The benefit of HHS was more pronounced if duration of untreated CA was >6 min or if initial rhythm was asystole or pulseless electrical activity (PEA). Negative side-effects were not observed after HHS. CONCLUSIONS: HHS after CA is feasible and safe and might improve short term survival after CPR. However, whether giving HHS could be a useful measure to increase resuscitation success after out-of-hospital CA requires a larger preclinical trial.

Effects of hypertonic versus isotonic infusion therapy on regional cerebral blood flow after experimental cardiac arrest cardiopulmonary resuscitation in pigs.

OBJECTIVE: To evaluate the effects of hypertonic, isooncotic, and isotonic infusion therapy on cerebral blood flow (CBF) during and after cardiopulmonary resuscitation (CPR) from experimental cardiac arrest (CA). METHODS: In 32 domestic swine (13-23 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either hypertonic saline (HS: 7.2% NaCl), hypertonic-isooncotic HES-saline (HHS: 7.2% NaCl in 6% HES 200,000/0.5), isooncotic HES (6% HES 200,000/0.5), or isotonic (normal) saline (NS: 0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure CBF quantitatively before CA, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation (ROSC). RESULTS: In HES/NaCl treated animals, CBF significantly decreased during CPR compared to the prearrest level (P < 0.01, respectively; MANOVA). In contrast, CBF was sustained during CPR in HS/HHS treated animals and significantly higher compared to animals receiving NS (P < 0.05, respectively). During recirculation severe postischaemic hypoperfusion as indicated by a decrease of CBF below the prearrest level, was present only in animals receiving HES and NS. CONCLUSIONS: Hypertonic solutions (HS/HHS) applied during internal cardiac massage enhanced CBF during CPR and after ROSC.

Time course of circulatory and metabolic recovery of cat brain after cardiac arrest assessed by perfusion- and diffusion-weighted imaging and MR-spectroscopy.

Brain recovery after cardiac arrest (CA) was assessed in cats using arterial spin tagging perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), and 1H-spectroscopy (1H-MRS). Cerebral reperfusion and metabolic recovery was monitored in the cortex and in basal ganglia for 6 h after cardiopulmonary resuscitation (CPR). Furthermore, the effects of an hypertonic/hyperoncotic solution (7.5% NaCl/6% hydroxyl ethyl starch, HES) and a tissue-type plasminogen activator (TPA), applied during CPR, were assessed on brain recovery. CA and CPR were carried out in the MR scanner by remote control. CA for 15-20 min was induced by electrical fibrillation of the heart, followed by CPR using a pneumatic vest. PWI after successful CPR revealed initial cerebral hyperperfusion followed by delayed hypoperfusion. Initial cerebral recirculation was improved after osmotic treatment. Osmotic and thrombolytic therapy were ineffective in ameliorating delayed hypoperfusion. Calculation of the apparent diffusion coefficient (ADC) from DWI demonstrated complete recovery of ion and water homeostasis in all animals. 1H-MRS measurements of lactate suggested an extended preservation of post-ischaemic anaerobic metabolism after TPA treatment. The combination of noninvasive MR techniques is a powerful tool for the evaluation of therapeutical strategies on circulatory and metabolic cerebral recovery after experimental cerebral ischaemia.

Hypertonic saline improves myocardial blood flow during CPR, but is not enhanced further by the addition of hydroxy ethyl starch.

OBJECTIVE: To evaluate the effects of hypertonic saline (HS) and/or hydroxy ethyl starch (HES) on myocardial perfusion pressure (MPP) and blood flow (MBF), and cardiac index (CI) during and after cardiopulmonary resuscitation (CPR). METHODS: In 32 domestic swine (13-23.5 kg) open chest CPR was initiated after 8 min of ventricular fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min of either HS (7.2% NaCl) or hypertonic HES saline (HHS) (6% HES 200000/0.5 in 7.2% NaCl) or HES (6% HES 200000/0.5 in 0.9% NaCl) or normal saline (NS) (0.9% NaCl). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure MBF and CI before cardiac arrest, during CPR, and 20, 90 and 240 min after restoration of spontaneous circulation. RESULTS: During CPR HS and HHS significantly increased MBF in comparison to HES and NS (P<0.05, respectively, MANOVA). MPP and CI were not different between the groups. HS and HHS significantly increased resuscitation success and the 240 min survival rate. 14/15 animals receiving HS or HHS and 8/17 after HES-or NS -infusion survived the observation period (P<0.05, chi(2)-test). No negative side effects of HS with or without the addition of HES were observed. CONCLUSIONS: Hypertonic solutions (HS and HHS) applied during internal cardiac massage enhanced MBF and significantly increased resuscitation success and survival rate. Addition of HES to HS did not further improve the positive haemodynamic effects of HS alone.

Effects of hypertonic saline on myocardial blood flow in a porcine model of prolonged cardiac arrest.

OBJECTIVE: To evaluate the effects of hypertonic saline (HS) on myocardial reperfusion pressure (MPP) and blood flow (MBF), and cardiac index (CI) during and after cardiopulmonary resuscitation (CPR). METHODS: In 21 domestic swine (16-23 kg) open chest cardiac massage was initiated after 10 min of ventricular fibrillation. With the onset of CPR animals randomly received HS (7.2%; 2 ml/kg per 10 min or 4 ml/kg per 20 min) or normal saline ((NS); 2 ml/kg per 10 min). Haemodynamic variables were monitored continuously, and coloured microspheres were used to measure MBF and CI before cardiac arrest (CA), during CPR and 5, 30 and 120 min after the return of spontaneous circulation. RESULTS: During CPR HS significantly increased MPP, MBF, and CI in comparison to NS (P<0.05, resp., MANOVA). Doubling the volume of HS did not improve the haemodynamic effects seen after application of 2 ml/kg per 10 min. HS-infusion significantly increased the survival rate at 120 min, 6/7 and 5/7 animals receiving 2 ml/kg per 10 min or 4 ml/kg per 20 min versus 2/7 after NS-infusion (P<0.05, chi(2)-test). CONCLUSIONS: HS applied during open chest cardiac massage enhanced MBF and CI, and significantly increased resuscitation success and survival rate. The positive effects of this promising new approach need to be confirmed in clinical studies.