Ernst Pfenninger

Effects of active compression-decompression resuscitation on myocardial and cerebral blood flow in pigs.

BACKGROUND This study was designed to assess the effects of a modified cardiopulmonary resuscitation (CPR) technique that consists of both active compression and active decompression of the chest (ACD CPR) versus standard CPR (STD CPR) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration. METHODS AND RESULTS During a 30-second period of ventricular fibrillation cardiac arrest, 14 pigs were randomized to receive either STD CPR (n = 7) or ACD CPR (n = 7). Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum, designed to provide either active chest compression (1.5 to 2.0 in.) and decompression or only active compression of the chest at 80 compressions per minute and 50% duty cycle. Using radiolabeled microspheres, median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 (7 to 30, minimum to maximum) STD CPR versus 30 (9 to 46) mL.min-1 x 100 g-1 with ACD CPR (P < .05). Median cerebral blood flow was 15 (10 to 26) mL.min-1 x 100 g-1 with STD CPR and 30 (21 to 39) with ACD CPR (P < .01). When comparing STD with ACD CPR, aortic systolic (62 mm Hg [48 to 70] vs 80 [59 to 86]) and diastolic (22 [18 to 28] vs 28 [21 to 36]) pressures, calculated coronary systolic (30 [22 to 36] vs 49 [37 to 56]) and diastolic (18 [16 to 23] vs 26 [21 to 31]) perfusion pressures, end-tidal CO2 (1.4% [0.8 to 1.8] vs 2.1 (1.8 to 2.4]), cerebral O2 delivery (3.1 mL.min-1 x 100 g-1 [1.5 to 4.5] vs 5.3 [3.8 to 7.5]), and cerebral perfusion pressure (14 mm Hg [4 to 22] vs 26 [6 to 34]) were all significantly higher with ACD CPR: To compare these parameters before and after vasopressor therapy, a bolus of high-dose epinephrine (0.2 mg/kg) was given to all animals after 5 minutes of ventricular fibrillation. Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine. The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later, once the acute effects of epinephrine had decreased. No difference in short-term resuscitation success was found between the two groups. CONCLUSIONS We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR:

Effect of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation

Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation.

Guidelines for the Treatment of Acidaemia with THAM

SummaryTHAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37°C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia.THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function.Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein; THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration.The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) × base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient).When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH ≤7.20), the use of THAM within a ‘therapeutic window’ is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi.THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary resuscitation

This study was designed to assess the interference by closed-chest cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG signal in a porcine model of cardiac arrest and to elucidate which variable of VF spectral analysis reflects best myocardial blood flow and resuscitation success during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR. Using radiolabeled microspheres, myocardial blood flow was determined during CPR before, and 90 s and 5 min after, drug administration. Using spectral analysis of VF, the median frequency, dominant frequency, edge frequency and amplitude of VF were determined simultaneously and before the first defibrillation attempt. Using filters in order to specify frequency ranges, stepwise elimination of mechanical artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz, median fibrillation frequency has a sensitivity, specificity, positive and negative predictive value of 100% to differentiate between resuscitated and non-resuscitated animals. The best correlation between myocardial blood flow and fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We conclude that spectral analysis of VF can provide reliable information relating to successful resuscitation. In this model after elimination of oscillations due to mechanical CPR, median fibrillation frequency best reflects the probability of resuscitation success.

Cognitive Impairment after Small-dose Ketamine Isomers in Comparison to Equianalgesic Racemic Ketamine in Human Volunteers

Background Ketamine is increasingly used in pain therapy but may impair brain functions. Mood and cognitive capacities were compared after equianalgesic small-dose S (+)-, R (−)-, and racemic ketamine in healthy volunteers. Methods Twenty-four subjects received intravenous 0.5 mg/kg racemic, 0.25 mg/kg S (+)-, and 1.0 mg/kg R (−)-ketamine in a prospective, randomized, double-blind, crossover study. Hemodynamic variables, mood, and cognitive capacities were assessed for 60 min. Results Transient increases in blood pressure, heart rate, and catecholamines were similar after administration of all drugs. At 20 min after injection, subjects felt less decline in concentration and were more brave after S (+)- than racemic ketamine. They reported being less lethargic but more out-of-control after R (−)- than racemic ketamine. Ketamine isomers induced less drowsiness, less lethargy, and less impairment in clustered subjective cognitive capacity than racemic ketamine for the 60-min study. Objective concentration capacity [test time, S (+): 25.4 ± 15.2 s, R (−): 34.8 ± 18.4 s, racemic ketamine: 40.8 ± 20.8 s, mean ± SD] and retention in primary memory [test time, S (+): 4.6 ± 1.2 s, R (−): 4.2 ± 1.4 s, racemic ketamine: 4.0 ± 1.4 s, mean ± SD] declined less after S (+)- than either R (−)- or racemic ketamine at 1 min. At 5 min, immediate recall, anterograde amnesia, retention in primary memory, short-term storage capacity, and intelligence quotient were less reduced after the isomers than racemic ketamine. Speed reading and central information flow decreased less after S (+)- than racemic ketamine. Conclusions Early after injection, ketamine isomers induce less tiredness and cognitive impairment than equianalgesic small-dose racemic ketamine. In addition, S (+)-ketamine causes less decline in concentration capacity and primary memory. The differences in drug effects cannot be explained by stereoselective action on one given receptor.

The effects of ketamine-isomers on neuronal injury and regeneration in rat hippocampal neurons

There is a difference in the relative anesthetic potency of the isomers of ketamine.Neuroprotective differences may therefore also exist. After an 8-min exposure to 500 micro Meter glutamate or axonal transection, cultured rat hippocampal neurons were maintained untreated or in the presence of ketamine-racemate, S(+)-ketamine, or R(-)-ketamine (10-4 M, 10-5 M, 10-6 M). Cell survival was examined by dye inclusion/esterase activity, morphology by phase contrast and immunofluorescence microscopy, and [(3) H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [(3) H]ARA increased fivefold. Dendritic length and branching decreased to a quarter and axonal extensions to the half. Ketamine-racemate 10-4 M increased survival to 65%, and induced longer dendrites (P <or=to 0.05). S(+)-Ketamine 10-4 M increased survival to 80%, reduced [(3) H]ARA threefold, and preserved cytoskeletal arborizations (P <or=to 0.05). Axotomy decreased survival to 60% and caused a minor increase in [(3) H]ARA after 7 days. Survival was 80% after 10-4 M ketamine-racemate and 90% after 10-4 M S(+)-ketamine (P <or=to 0.05). Only S(+)-ketamine supported axonal reoutgrowth and decreased [(3) H]ARA (P <or=to 0.05). R(-)-Ketamine was ineffective after both types of injury. Ketamine-racemate and S(+)-ketamine attenuated injury after glutamate exposure or axonal transection in hippocampal neurons in vitro. Neuroregenerative effects were uniquely demonstrated by S(+)-ketamine. (Anesth Analg 1996;83:505-12)

EFFECTS OF EPINEPHRINE AND VASOPRESSIN ON MEDIAN FIBRILLATION FREQUENCY AND DEFIBRILLATION SUCCESS IN A PORCINE MODEL OF CARDIOPULMONARY RESUSCITATION

OBJECTIVE This study was designed to assess whether median frequency of ventricular fibrillation (VF) correlates with myocardial blood flow and defibrillation success during cardiopulmonary resuscitation (CPR) after epinephrine or vasopressin administration. METHODS AND RESULTS After 4 min of VF and 3 min of CPR, 14 pigs received 0.045 mg/kg epinephrine or 0.4 U/kg vasopressin. Using radio-labeled microspheres, median myocardial blood flow during CPR before, and 90 s and 5 min after drug administration (DA) was 15.5 (12.6, 23.1; 25th percentile, 75th percentile), 26.4 (18.5, 29.1), 16.9 (14.9, 19.1) mL min-1 100 g-1, respectively, in the epinephrine, and 16.9 (15.4, 18.9), 48.1 (36.9, 68.9) (P < 0.05 vs. before DA), 52.3 (38.5, 65.0) mL min-1 100 g-1, respectively, in the vasopressin group. Using spectral analysis of VF, median frequency of VF was 11.0 (10.7, 11.8), 11.3 (9.6, 13.1), 10.2, (8.8, 11.4) Hz, respectively, in the epinephrine, and 10.1 (10.0, 10.5), 11.7 (11.1, 14.2) (P < 0.05 vs. before DA), 13.2 (11.5, 13.9) Hz, respectively, in the vasopressin group at the same points in time. Median frequency correlates significantly with myocardial blood flow in the epinephrine (n = 21); rs = 0.772; P < 0.001) and in the vasopressin group (n = 21; rs = 0.905; P < 0.001). Median fibrillation frequency before the first defibrillation was 13.0 (12.2, 13.2) Hz in resuscitated (n = 8) and 9.2 (8.3, 10.2) Hz (n = 6) in non-resuscitated animals (P < 0.01). CONCLUSIONS We conclude that median frequency of VF reflects myocardial blood flow and the chance of successful defibrillation during closed-chest CPR after vasopressor treatment in a porcine model of VF.

Effects of graded doses of vasopressin on median fibrillation frequency in a porcine model of cardiopulmonary resuscitation: results of a prospective, randomized, controlled trial.

OBJECTIVE To assess the effects of graded doses of vasopressin vs. saline on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. DESIGN Prospective, randomized, controlled trial. SETTING Animal laboratory in a university medical center. SUBJECTS Twenty-eight domestic pigs (body weight between 26 and 31 kg), aged 12 to 14 wks. INTERVENTIONS AND MAIN RESULTS After 4 mins of ventricular fibrillation and 3 mins of closed-chest cardiopulmonary resuscitation, the animals were allocated to receive either 0.2 U/kg of vasopressin (n = 7), 0.4 U/kg of vasopressin (n = 7), 0.8 U/kg of vasopressin (n = 7), or 10 mL of saline (n = 7, control group). Using radiolabeled microspheres, myocardial blood flow rates during cardiopulmonary resuscitation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups (mean +/- SEM): 18.8 +/- 0.9, 17.2 +/- 1.1, and 14.6 +/- 1.4 mL/min/100 g in the control group; 17.8 +/- 2.2, 49.6 +/- 6.3 (p < .01 vs. control group), and 29.4 +/- 3.1 mL/min/100 g (p < .05 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 17.1 +/- 1.0, 52.4 +/- 7.5 (p < .01 vs. control group), and 52.2 +/- 5.8 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 18.1 +/- 1.6, 94.9 +/- 9.2 (p < .001 vs. control group), and 57.2 +/- 6.3 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin. Using spectral analysis, median frequencies of ventricular fibrillation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups: 9.6 +/- 0.4, 8.5 +/- 0.8, and 7.2 +/- 1.0 Hz in the control group; 9.7 +/- 0.5, 12.9 +/- 0.8 (p < .01 vs. control group), and 12.7 +/- 0.8 Hz (p < .001 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 10.3 +/- 0.2, 12.7 +/- 0.9 (p < .01 vs. control group), and 12.8 +/- 0.7 Hz (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 10.0 +/- 0.9, 14.1 +/- 0.9 (p < .001 vs. control group), and 12.5 +/- 0.9 Hz (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin at the same points in time. Median frequency before the first defibrillation attempt was 12.3 +/- 0.4 Hz in the resuscitated animals (n = 19) and 8.2 +/- 1.2 Hz in the nonresuscitated animals (n = 9) (p < .001). CONCLUSIONS This study contributes to the characterization of the effect of increasing global myocardial blood flow on median fibrillation frequency after administration of graded doses of vasopressin in a porcine model of ventricular fibrillation. Interventions such as vasopressor treatment that increase fibrillation frequency improve the chance of successful defibrillation.

Medical student disaster medicine education: the development of an educational resource

BackgroundDisaster medicine education is an enormous challenge, but indispensable for disaster preparedness.AimsWe aimed to develop and implement a disaster medicine curriculum for medical student education that can serve as a peer-reviewed, structured educational guide and resource. Additionally, the process of designing, approving and implementing such a curriculum is presented.MethodsThe six-step approach to curriculum development for medical education was used as a formal process instrument. Recognized experts from professional and governmental bodies involved in disaster health care provided input using disaster-related physician training programs, scientific evidence if available, proposals for education by international disaster medicine organizations and their expertise as the basis for content development.ResultsThe final course consisted of 14 modules composed of 2-h units. The concepts of disaster medicine, including response, medical assistance, law, command, coordination, communication, and mass casualty management, are introduced. Hospital preparedness plans and experiences from worldwide disaster assistance are reviewed. Life-saving emergency and limited individual treatment under disaster conditions are discussed. Specifics of initial management of explosive, war-related, radiological/nuclear, chemical, and biological incidents emphasizing infectious diseases and terrorist attacks are presented. An evacuation exercise is completed, and a mass casualty triage is simulated in collaboration with local disaster response agencies. Decontamination procedures are demonstrated at a nuclear power plant or the local fire department, and personal decontamination practices are exercised. Mannequin resuscitation is practiced while personal protective equipment is utilized. An interactive review of professional ethics, stress disorders, psychosocial interventions, and quality improvement efforts complete the training.ConclusionsThe curriculum offers medical disaster education in a reasonable time frame, interdisciplinary format, and multi-experiential course. It can serve as a template for basic medical student disaster education. Because of its comprehensive but flexible structure, it should also be helpful for other health-care professional student disaster education programs.

The effect of ketamine on intracranial pressure during haemorrhagic shock under the conditions of both spontaneous breathing and controlled ventilation

SummarySeventeen piglets of both sexes, seven with O2/air-buprenorphine anaesthesia and controlled ventilation, and ten unanaesthetized animals with normal, spontaneous respiration, were used for the study. The intracranial pressure of both groups of animals was raised by insufflation of an epidural ballon and the arterial blood pressure was reduced to approximately 70% of the original value by controlled haemorrhage. 0.5 mg/kg body weight of ketamine was given intravenously, followed by a further dose of 2.0 mg/kg body weight of ketamine five minutes later.Both ketamine doses led to a significant rise in the intracranial pressure of those animals breathing spontaneously (31.8 mm Hg to 39.1 mm Hg). In contrast, the ventilated animals showed a significant reduction in intracranial pressure. No changes in arterial PCO2 were observed in this group, while those piglets breathing spontaneously had dangerous PCO2 rises. At both ketamine doses a significant correlation could be found between the PCO2 and the intracranial pressure.