Karl H. Stadlbauer

Vasopressin, but Not Fluid Resuscitation, Enhances Survival in a Liver Trauma Model with Uncontrolled and Otherwise Lethal Hemorrhagic Shock in Pigs

Background: The authors compared the effects of vasopressin versus fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. Methods: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n 9), or fluid resuscitation (n 7), or saline placebo (n 7), respectively. A continuous infusion of 0.08 U·k g 1 · min 1 vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed. Results: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean SD, 72 26 vs. 38 16 vs. 11 7 mmHg, respectively; P < 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressintreated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (~15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 6 vs. 42 4 vs. 43 6 ml/kg, respectively; P < 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05). Conclusions: Vasopressin, but not fluid resuscitation or saline placebo, ensured survival with full recovery in this liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.

Signs of inflammation after sciatic nerve block in pigs

Nerve stimulators are widely used to assist with peripheral nerve blocks but do not eliminate the risk of nerve injury. We evaluated the histologic findings 6 h after sciatic nerve block with bupivacaine in pigs. When a motor response was still obtained with a current <0.2 mA (n = 10), the postmortem microscopic evaluation revealed lymphocytes and granulocytes sub-, peri-, and intraneurally in 5 (50%) of 10 pigs. No signs of inflammation were observed when the muscle contraction was achieved with a current between 0.3 and 0.5 mA (P = 0.03). In conclusion, the current required to elicit a motor response, the position of the needle tip, and the subsequent likelihood of nerve damage merit further evaluation.

Vasopressin during uncontrolled hemorrhagic shock: less bleeding below the diaphragm, more perfusion above.

I n 1990, about 5 million people died worldwide as a result of injury, and it seems likely that the global epidemic of deadly trauma is only beginning. By 2020, deaths from injury are expected to increase to 8 million worldwide (2), and 30% of these fatalities will be attributable to uncontrolled hemorrhagic shock (3). Resuscitation of patients in uncontrolled hemorrhagic shock remains one of the most challenging aspects of emergency care, and trauma patients with complete cardiovascular collapse have an extremely poor chance of survival. For example, in a 1993 study of 138 trauma patients requiring cardiopulmonary resuscitation at the accident scene or during transport, none of the initially successfully resuscitated patients survived to hospital discharge (4). Accordingly, prevention of cardiac arrest has been considered to be the primary goal of trauma care (5). Unfortunately, trauma-related cardiac arrest is only the tip of the iceberg. Because hemorrhage-induced hypotension in trauma patients is predictive of frequent mortality and morbidity (6), fighting prolonged hypotension may be equally important. For hemodynamic stabilization of critically injured patients with uncontrolled hemorrhagic shock current trauma guidelines recommend infusion of crystalloid or colloid solutions in addition to catecholamine vasopressors. In a large clinical study of penetrating torso trauma, patients receiving delayed fluid resuscitation had better survival rates than those receiving immediate fluid resuscitation (7). Roberts et al. (8) further found no scientific evidence for the effectiveness of immediate fluid resuscitation in uncontrolled hemorrhagic shock. And a Cochrane review of randomized controlled trials found no evidence either for or against early or large volume IV fluid administration in uncontrolled hemorrhage (9). At present, therefore, we have no clearly proven fluid resuscitation strategy for uncontrolled hemorrhagic shock, and it seems expedient to consider alternative strategies to prevent immediate or delayed cardiac arrest in these patients. There are experimental and clinical data showing promising effects of infusing vasopressin in severe hemorrhagic shock. For example, vasopressin improved shortand long-term survival in a porcine model of uncontrolled hemorrhagic shock after penetrating liver trauma (10,11). In patients with intraabdominal bleeding and subsequent shock which was unresponsive to volume replacement, vasopressin was reported to be beneficial to stabilize cardiocirculatory status almost 20 yr ago (12). In addition to the strong vasopressor effect of vasopressin during catecholamine-refractory shock, another beneficial effect of vasopressin may be that blood is shifted away from a given subdiaphragmatic site of injury to the heart and brain, thus decreasing bleeding and optimizing vital organ perfusion. This specific effect of vasopressin may be especially life-saving in patients with uncontrolled hemorrhage resulting from subdiaphragmatic injury. In agreement with this hypothesis, we observed beneficial effects of vasopressin in both blunt and penetrating trauma patients with uncontrolled hemorrhagic shock (13) and were able to resuscitate a blunt trauma patient with uncontrolled hemorrhagic shock (14). Despite these promising observations, some researchers are concerned about vasopressin-related problems such as negative cardiac inotropy and myocardial ischemia (15,16), and others have questioned Data from a previous study (1) are being used for a vasopressin registration application process by Aguettant, Lyon, France, in Europe. Aguettant has once supported our working group with grant support. No author has a financial interest in drugs being discussed in this manuscript. Supported by science project no. 10618 and 9513 of The Austrian National Bank, Vienna, Austria. Accepted for publication April 20, 2005. Address correspondence to Karl H. Stadlbauer, MD, Innsbruck Medical University, Department of Anesthesiology and Critical Care Med, Anichstrasse 35, 6020 Innsbruck, Austria. Address electronic mail to karl-heinz.stadlbauer@uibk.ac.at. Address reprint requests to Karl H. Lindner, MD, Innsbruck Medical University, Department of Anesthesiology and Critical Care Medicine, Anichstrasse 35, 6020 Innsbruck, Austria.

A pilot study to evaluate the SMART BAG®: A new pressure-responsive, gas-flow limiting bag-valve-mask device

Reducing inspiratory flow rate and peak airway pressure may be important to minimize the risk of stomach inflation when ventilating an unprotected airway with positive pressure ventilation. In this study, we assessed the effects of a standard self-inflating bag compared with a new pressure-responsive, inspiratory gas flow-limiting device (SMART BAG®) on respiratory mechanics in 60 adult patients undergoing routine induction of anesthesia. Respiratory variables were measured using a pulmonary monitor. The SMART BAG® resulted in significantly decreased inspiratory flow rate and peak airway pressure while providing adequate tidal volume delivery.

Decreasing peak flow rate with a new bag-valve-mask device: effects on respiratory mechanics, and gas distribution in a bench model of an unprotected airway.

Reducing inspiratory flow rate and peak airway pressure may be important in order to minimise the risk of stomach inflation when ventilating an unprotected airway with positive pressure ventilation. The purpose of this study was to assess the effects of a newly developed bag-valve-mask device (SMART BAG), O-Two Systems International, Ont., Canada) that limits peak inspiratory flow. A bench model simulating a patient with an unintubated airway was used consisting of a face mask, manikin head, training lung (lung compliance, 100 ml/cm H(2)O, airway resistance 4 cm H(2)O/l/s, lower oesophageal sphincter pressure 20 cm H(2)O and simulated stomach). Twenty nurses were randomised to each ventilate the manikin using a standard single person technique for 1 min (respiratory rate, 12/min) with either a standard adult self-inflating bag, or the SMART BAG. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The SMART BAG vs. standard self-inflating bag resulted in significantly (P<0.05) lower mean+/-S.D. peak inspiratory flow rates (32+/-2 vs. 61+/-13 l/min), peak inspiratory pressure (12+/-2 vs. 17+/-2 cm H(2)O), lung tidal volumes (525+/-111 vs. 680+/-154 ml) and stomach tidal volumes (0+/-0 vs. 17+/-36 ml), longer inspiratory times (1.9+/-0.3 vs. 1.5+/-0.3 s), but significantly higher mask leakage (26+/-13 vs. 14+/-8%); mask tidal volumes (700+/-104 vs. 785+/-172 ml) were comparable. The mask leakage observed is not an uncommon factor in bag-valve-mask ventilation with leakage fractions of 25-40% having been previously reported. The differences observed between the standard BVM and the SMART BAG are due more to the anatomical design of the mask and the non-anatomical shape of the manikin face than the function of the device. Future studies should remove the mask to manikin interface and should introduce a standardized mask leakage fraction. The use of a two-person technique may have removed the problem of mask leakage. In conclusion, using the SMART BAG during simulated ventilation of an unintubated patient in respiratory arrest significantly decreased inspiratory flow rate, peak inspiratory pressure, stomach tidal volume, and resulted in a significantly longer inspiratory time when compared to a standard self-inflating bag.

Vasopressin During Cardiopulmonary Resuscitation and Different Shock States

Vasopressin administration may be a promising therapy in the management of various shock states. In laboratory models of cardiac arrest, vasopressin improved vital organ blood flow, cerebral oxygen delivery, the rate of return of spontaneous circulation, and neurological recovery compared with epinephrine (adrenaline). In a study of 1219 adult patients with cardiac arrest, the effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity; however, vasopressin was superior to epinephrine in patients with asystole. Furthermore, vasopressin followed by epinephrine resulted in significantly higher rates of survival to hospital admission and hospital discharge. The current cardiopulmonary resuscitation guidelines recommend intravenous vasopressin 40IU or epinephrine 1mg in adult patients refractory to electrical countershock. Several investigations have demonstrated that vasopressin can successfully stabilize hemodynamic variables in advanced vasodilatory shock. Use of vasopressin in vasodilatory shock should be guided by strict hemodynamic indications, such as hypotension despite norepinephrine (noradrenaline) dosages >0.5βlg/kg/min. Vasopressin must never be used as the sole vasopressor agent. In our institutional routine, a fixed vasopressin dosage of 0.067 IU/min (i.e. 100 IU/50mL at 2 mL/h) is administered and mean arterial pressure is regulated by adjusting norepinephrine infusion. When norepinephrine dosages decrease to 0.2βg/kg/min, vasopressin is withdrawn in small steps according to the response in mean arterial pressure. Vasopressin also improved short-and long-term survival in various porcine models of uncontrolled hemorrhagic shock. In the clinical setting, we observed positive effects of vasopressin in some patients with life-threatening hemorrhagic shock, which had no longer responded to adrenergic catecholamines and fluid resuscitation. Clinical employment of vasopressin during hemorrhagic shock is experimental at this point in time.

Vasopressin improves survival in a porcine model of abdominal vascular injury

IntroductionWe sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs.MethodsDuring general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringers and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.ResultsAfter 68 ± 19 min (mean ± standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).ConclusionVasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.

The effects of nifedipine on ventricular fibrillation mean frequency in a porcine model of prolonged cardiopulmonary resuscitation.

We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during prolonged cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety seconds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P < 0.01) increased in nifedipine versus placebo pigs (mean ± sd: 12.4 ± 2.1 Hz versus 8 ± 0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventricular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P < 0.05) increased in nifedipine versus placebo animals (9.7 ± 1.2 Hz versus 7.1 ± 1.3 Hz). Coronary perfusion pressure was significantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclusion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at ∼10 Hz during prolonged CPR; this was nevertheless associated with no defibrillation success.

A suction laryngoscope facilitates intubation for physicians with occasional emergency medical service experience—A manikin study with severe simulated airway haemorrhage ☆ ☆☆

INTRODUCTION We developed a suction laryngoscope, which enables simultaneous suction and laryngoscopy in cases of airway haemorrhage and evaluated its potential benefits in physicians with varying emergency medical service experience. METHODS Eighteen physicians with regular and 24 physicians with occasional emergency medical service experience intubated the trachea of a manikin with severe simulated airway haemorrhage using the suction laryngoscope and the Macintosh laryngoscope in random order. RESULTS In physicians with regular emergency medical service experience, there was neither a difference in time needed for intubation [median (IQR, CI 95%)]: 34 (18, 30-46) vs. 34 (22, 30-52) s; P=0.52, nor in the number of oesophageal intubations [0/18 (0%) vs. 3/18 (16.7%); P=NS] when using the suction vs. the Macintosh laryngoscope. In physicians with occasional emergency medical service experience, there was no difference in time needed for intubation [median (IQR, CI 95%)]: 42 (25, 41-57) vs. 45 (33, 41-65) s; P=0.56, but the number of oesophageal intubations was significantly lower when using the suction laryngoscope [4/24 (16.7%) vs. 12/24 (50.0%); P=0.04]. CONCLUSIONS In a model of severe simulated airway haemorrhage, employing a suction laryngoscope significantly decreased the likelihood of oesophageal intubations in physicians with occasional emergency medical service experience.

Influence of negative expiratory pressure ventilation on hemodynamic variables during severe hemorrhagic shock.

Objective:Outcome after trauma with severe hemorrhagic shock is still dismal. Since the majority of blood is present in the venous vessels, it might be beneficial to perform venous recruiting via the airway during severe hemorrhagic shock. Therefore, the purpose of our study was to evaluate the effects of negative expiratory pressure ventilation on mean arterial blood pressure, cardiac output, and short-term survival during severe hemorrhagic shock. Design:Prospective study in 21 laboratory animals. Setting:University hospital research laboratory. Subjects:Tyrolean domestic pigs. Interventions:After induction of controlled hemorrhagic shock (blood loss ∼45 mL/kg), 21 pigs were randomly ventilated with either zero end-expiratory pressure (0 PEEP; n = 7), 5 cm H2O positive end-expiratory pressure (5 PEEP; n = 7), or negative expiratory pressure ventilation (up to −30 cm H2O at the endotracheal tube during expiration; n = 7). Measurements and Main Results:Mean (±sd) arterial blood pressure was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (38 ± 5 vs. 27 ± 3 mm Hg; p = .001) and the 5 PEEP animals (38 ± 5 vs. 20 ± 6 mm Hg; p < .001) after 5 mins of the experiment. Cardiac output was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (3.1 ± .4 vs. 1.9 ± .9 L/min; p = .001) and 5 PEEP animals (3.1 ± .4 vs. 1.2 ± .8 L/min; p < .001) after 5 mins of the experiment. All seven negative expiratory pressure ventilation animals, but only three of seven 0 PEEP animals (p = .022), survived the 120-min study period, whereas all seven of seven 5 PEEP animals were dead within 35 mins (p < .001). Limitations include that blood loss was controlled and that the small sample size limits the evaluation of survival outcome. Conclusions:When compared with pigs ventilated with either 0 PEEP or 5 PEEP, negative expiratory pressure ventilation during severe hemorrhagic shock improved mean arterial blood pressure and cardiac output.