James E. Manning

Bovine hemoglobin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine

In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringers solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringers and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringers swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringers and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringers and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringers in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.

Heart rates in fire fighters using light and heavy breathing equipment: Similar near-maximal exertion in response to multiple work load conditions

Intense exertion is an occupational hazard inherent to fire fighting. This study was designed to look at the exertion levels that fire fighters attain during a fire fighting exercise when using (1) no self-contained breathing apparatus (SCBA), (2) light SCBA, and (3) heavy SCBA. Exertion levels were measured as a function of the heart rate increase relative to the maximum predicted heart rate determined by a standard treadmill exercise test. Five fire fighters wore electrocardiographic monitors during a routine fire fighting exercise. Heart rates increased rapidly to 70% to 80% of maximum within the first minute and then plateaued at 90% to 100% until the attack on the fire was completed. There was no significant difference between exertion levels when using no SCBA, light SCBA, and heavy SCBA (split-plot analysis of variance, p greater than .25). These results suggest that fire fighters attain an intense level of physical activity quickly and maintain that level as long as they are actively engaged in fighting fire. These results also suggest that regardless of the weight of the SCBA, if employed, fire fighters exert themselves from 85% to 100% of their maximum and adjust their work output to maintain that near-maximal level.

HBOC-201 improves survival in a swine model of hemorrhagic shock and liver injury

BACKGROUND Blunt abdominal trauma that leads to hemorrhagic shock and cardiac arrest is almost always fatal in the prehospital setting. The current study investigated whether a hemoglobin-based oxygen carrier (HBOC-201) could maintain organ viability during an exsanguinating liver injury and allow for prolonged survival. This hypothesis was tested in a large animal model that simulated blunt abdominal trauma with major organ injury. METHODS Swine underwent a liver crush, laceration and 50 ml/kg initial blood loss. The liver bled at 3 ml/kg per min during the resuscitation phase. No fluid (NF=6), hetastarch (HES=8), or HBOC-201 (HBOC=8) was given during the resuscitation phase. Swine alive 60 min after the initial injury underwent liver repair and 96 h observation. RESULTS All HBOC swine survived 60 min versus none of the NF or HES swine (P<0.05). All HBOC swine survived 24 h and 7/8 survived 96 h with good functional recovery. CONCLUSIONS HBOC resuscitation during liver bleeding in a swine model of hemorrhagic shock and liver injury allowed for 96 h survival. No fluid or HES in the same model was fatal.

Selective aortic arch perfusion during cardiac arrest: A new resuscitation technique

STUDY OBJECTIVES To demonstrate the technique of selective aortic arch perfusion during cardiac arrest and to observe the hemodynamic effects of volume infusion and aortic epinephrine administration. DESIGN Sequential series, nonrandomized, noncontrolled. TYPE OF PARTICIPANTS Fourteen mongrel dogs weighing 21 to 36 kg. INTERVENTIONS Animals had midaortic arch pressure, right atrial pressure, and descending aortic arch balloon occlusion catheters placed. After ten minutes of ventricular fibrillation, balloon inflation and aortic arch infusions were initiated as follows: group 1 (six), 30 mL/kg/min of 0.9% NaCl for two minutes; group 2 (four), 30 mL/kg/min of oxygenated lactated Ringers with 2 mg/L epinephrine for two minutes, followed by CPR; and group 3 (four), 20 mL/kg/min of oxygenated perfluorochemicals with 4 mg/L epinephrine for one minute, then CPR. MEASUREMENTS AND MAIN RESULTS Midaortic arch pressure, right atrial pressure, and coronary perfusion pressure each rose significantly in all groups. Midaortic arch pressure and coronary perfusion pressure increases were greater in groups 2 and 3 than in group 1. In groups 1 and 2, right atrial pressure increases at end-selective aortic arch perfusion were excessive as midaortic arch pressure and right atrial pressure increased linearly and similarly after 20 to 30 seconds. In groups 2 and 3, CPR-diastolic midaortic arch pressure and coronary perfusion pressure after selective aortic arch perfusion were good and similar to midaortic arch pressure and coronary perfusion pressure at end-selective aortic arch perfusion. CONCLUSION Selective aortic arch perfusion is technically feasible, but excessive right atrial pressure increases limit maximal infusion rates and volumes. Selective aortic arch perfusion infusates with epinephrine produce greater midaortic arch pressure and coronary perfusion pressure during infusion than infusate without epinephrine. Controlled studies are needed to determine if selective aortic arch perfusion improves resuscitation outcome.

Pulse contour cardiac output analysis in a piglet model of severe hemorrhagic shock

Objective:Pulse contour cardiac output (PCCO) analysis is a technique for continuous cardiac output (CO) monitoring through an arterial catheter after calibration by transpulmonary thermodilution (TPTD). Studies in adults show good correlation with pulmonary artery thermodilution (PATD) CO. Data are limited in children and patients with hemodynamic instability. The objective was to determine whether TPTD CO and PCCO analysis correlate with PATD CO in a piglet model of severe hemorrhagic shock. Mixed venous oxygen saturation (S&OV0413;o2) was also compared with PATD CO. Design:Prospective animal study. Setting:University animal research laboratory. Subjects:Domesticated piglets, 24–37 kg. Interventions:Hemorrhagic shock was created by graded hemorrhage in anesthetized piglets. Hemorrhage was initiated to achieve mean arterial pressure plateaus of 60, 50, 40, 30, and 20 mm Hg. Measurements and Main Results:CO was measured by PATD and simultaneously with two femoral artery PCCO catheters. At each mean arterial pressure plateau, one PCCO catheter was recalibrated by TPTD; the other catheter was not recalibrated during hemorrhage. TPTD CO, PCCO measurements from each catheter, and S&OV0413;o2 were compared with PATD CO at each mean arterial pressure level. TPTD CO and recalibrated PCCO showed excellent correlation (r2 = .96 and .97) and small bias (+0.11 and +0.14 L/min), respectively, compared with PATD. Without recalibration, PCCO measurements were not accurate during rapid hemorrhage (r2 = .22). S&OV0413;o2 decline did not correlate as well with PATD CO (r2 = .69). Conclusions:TPTD CO and recalibrated PCCO analysis correlate well with PATD CO in this severe hemorrhagic shock model. The mean difference is small (<0.15 L/min) and is not clinically significant. With rapid changes in blood pressure or intravascular volume, PCCO is not accurate unless recalibrated by TPTD CO. S&OV0413;o2 did not correlate well with CO in this model.

Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine

Objective The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. Design Randomized, controlled, laboratory investigation. Setting University research laboratory. Subjects Domestic swine, 25–39 kg. Interventions Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10–13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer’s (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL·kg−1·min−1 until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mg/kg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). Measurements and Main Results Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 ± 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for <10 mins. One-hour survival was five of six in the SAAP-HBOC group and none of six in the SAAP-LR group (p < .05, Fisher’s exact test). Conclusion SAAP with oxygenated HBOC-201 rapidly restored viable cardiovascular function after exsanguinating cardiac arrest in this swine model of liver injury with profound hemorrhagic shock.

Selective aortic arch perfusion during cardiac arrest: enhanced resuscitation using oxygenated perflubron emulsion, with and without aortic arch epinephrine.

STUDY OBJECTIVE To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. METHODS This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. RESULTS Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1 +/- 1.9 minutes in the AoE-SAAP group, compared with 11.0 +/- 5.8 minutes in the IVE-SAAP group. CONCLUSION SAAP with oxygenated perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC.

Factors associated with prolongation of transport times of emergency pediatric patients requiring transfer to a tertiary care center

Purpose: The purpose of this study was to determine factors associated with longer times to transport of emergency pediatric patients requiring tertiary care. Design: Retrospective case series. Setting: Emergency pediatric transport service. Participants: Infants and children transported by the transport service at the University of North Carolina Hospitals at Chapel Hill from January 1, 1988, to December 31, 1990. Main measurements: The time-to-request, the time from patient arrival at the referring hospital to the time when the request for transfer was received, and the ground time, defined as the time between the transport teams arrival at the referring hospital and their departure, were recorded for each transported patient. Results: Three hundred consecutive children 0 to 16 years (61 % male) were transferred. Time-to-request was shorter for trauma patients (median 62 minutes, quartiles 29 and 153 minutes) than for medical patients (median 172 minutes, quartiles 83 and 508 minutes) (P=0.0001). Infants, children, and adolescents had similar times-to-request of 147 minutes, 129 minutes, and 128 minutes, respectively (P=0.91). Increased ground times were associated with diagnosis category (median of 40 minutes for medical patients vs 29 minutes for trauma patients) (P=0.0001), with younger age (median of 46 minutes for infants, 35 minutes for children, and 28 minutes for adolescents) (P=0.0001), and with the performance of major procedures (median of 35 minutes if no procedures were performed, 38 minutes if one procedure was performed, and 54 minutes if two procedures were performed) (P=0.039). After the transport team arrived, 13% (40/300) of patients required at least one major procedure prior to transport. Conclusions: Increased time-to-request for patients with medical diagnoses, increased ground times for younger patients and patients with medical diagnoses, and failure to perform necessary procedures contribute to a prolongation of the time-to-transport of emergency pediatric patients. The magnitude of the impact of these longer transport times on outcome is unknown.

Aortic arch versus central venous epinephrine during CPR

STUDY OBJECTIVE To determine if delivery of epinephrine to the peripheral arterial system by an aortic arch catheter is more effective than central venous epinephrine administration during cardiac resuscitation. DESIGN Randomized, nonblinded, controlled trial. TYPE OF PARTICIPANTS Sixteen mongrel canines (25 to 31 kg). INTERVENTIONS Animals had aortic arch pressure, and right atrial pressure, superior vena cava infusion, and descending aortic arch infusion catheters placed using fluoroscopy. After ten minutes of ventricular fibrillation, three DC countershocks were delivered over one minute. If unsuccessful, CPR at 120 compressions per minute was begun, and at 60 seconds of CPR, epinephrine (1 mg/50 mL normal saline) was administered either through the superior vena cava or the aortic arch catheter followed by one more minute of CPR. Defibrillation then was attempted and, if unsuccessful, further resuscitative efforts followed advanced cardiac life support guidelines, except route and dose of epinephrine remained the same. MEASUREMENTS AND MAIN RESULTS Aortic arch pressure, right atrial pressure, and coronary perfusion pressure (diastolic aortic arch pressure minus diastolic right atrial pressure) were recorded continuously. Aortic arch pressure and coronary perfusion pressure increased more rapidly and to a greater magnitude with aortic arch-epinephrine than superior vena cava-epinephrine. Coronary perfusion pressure doubled by ten seconds in seven of eight in the aortic arch-epinephrine group versus none in the superior vena cava-epinephrine group. Aortic arch pressure and coronary perfusion pressure increases consistently plateaued within 60 seconds after aortic arch-epinephrine but not after superior vena cava-epinephrine. Return of spontaneous circulation was faster (P < .05) in the aortic arch-epinephrine group. Maximal coronary perfusion pressure after epinephrine correlated with the coronary perfusion pressure immediately before epinephrine administration in both groups, but more strongly in the aortic arch-epinephrine group (P = .0001). CONCLUSION For an equivalent dose of epinephrine, aortic arch administration produces a more rapid response and more rapid peak effect than central venous administration. The combination of aortic arch-epinephrine administration and aortic pressure monitoring may be useful when initial standard resuscitative measures have not been successful.

Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation

BACKGROUND Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction. METHODS AND RESULTS Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC+NTG10 mcg/kg/min, HBOC+NTG20 mcg/kg/min, HBOC+NTG40 mcg/kg/min, Hetastarch (HES), HES+NTG20 mcg/kg/min, NTG20 mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP=94+/-33 mmHg), mean pulmonary artery pressure (MPAP=29+/-11 mmHg) and systemic vascular resistance (SVR=2684+/-871 dyns/cm(5)) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC+40 mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP=59+/-23 mmHg, MPAP=18+/-7 mmHg, and SVR=1827+/-511 dyns/cm(5)), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation. CONCLUSION Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.