Open Access Open Access  Restricted Access Subscription or Fee Access

Intraosseous hydroxocobalamin versus intravenous hydroxocobalamin compared to intraosseous whole blood or no treatment for hemorrhagic shock in a swine model

Vikhyat S. Bebarta, MD, FACEP, FACMT, Normalynn Garrett, PhD, Susan Boudreau, RN, BSN, Maria Castaneda, MS

Abstract


Objective: To determine if intraosseous (IO) hydroxocobalamin can improve systolic blood pressure (SBP) in a swine model after severe hemorrhagic shock.

Methods: Thirty six swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring and then hemorrhaged such that 30 percent of their blood volume was extracted over 20 minutes. Five minutes later, animals were randomly assigned to receive 500 mL IO whole blood, 150 mg/kg IO or intravenous (IV) hydroxocobalamin in 180 mL of saline, or no treatment and then monitored for 60 minutes. A sample size of eight animals per group was based on a power of 80 percent, an alpha of 0.05, and a small effect size to detect a difference in SBP between groups. Outcome data were analyzed using repeated measures analysis of variance (RMANOVA).

Results: RMANOVA outcome analysis detected a significant difference between groups (p < 0.05). IO whole blood, IO hydroxocobalamin, and IV hydroxocobalamin groups were similar to each other, but significantly different compared to controls regarding SBP, mean arterial pressure (MAP), systemic vascular resistance, and heart rate. Differences in SBP and MAP were sustained throughout the experiment. At 60 minutes, the comparison among the groups, IO whole blood, IO hydroxocobalamin, IV hydroxocobalamin, and control, was the following: SBP 78.2 versus 83.7 versus 75.1 versus 55.3 mm Hg; MAP 62.7 versus 65 versus 60 versus 43 mm Hg. There was a significant interaction by time in lactate values (p < 0.01) such that control animal lactate values increased over time (3.3 mmol/L) compared to IO whole blood, IO or IV hydroxocobalamin treated animals (1.1, 1.6, 1.3 mmol/L).

Conclusions: IO hydroxocobalamin improved SBP, MAP, compared to no treatment and was similar to IO whole blood and IV hydroxocobalamin in this animal model of severe hemorrhage. Moreover, whereas serum lactate was improving in all treated groups, it was deteriorating in the control group.


Keywords


hydroxocobalamin, intraosseous infusion, swine, hemorrhage, resuscitation

Full Text:

PDF

References


Kisat M, Morrison JJ, Hashmi ZG, et al.: Epidemiology and outcomes of non-compressible torso hemorrhage. J Surg Res. 2013; 184: 414-421.

TCCC Guidelines and Curriculum [serial online]. 2012. Available at http://www.naemt.org/education/TCCC/guidelines_curriculum.aspx. Accessed February 17, 2015.

Lairet JR, Bebarta VS, Burns CJ, et al.: Prehospital interventions performed in a combat zone: A prospective multicenter study of 1,003 combat wounded. J Trauma Acute Care Surg. 2012; 73: S38-S42.

Wafaisade A, Wutzler S, Lefering R, et al.: Drivers of acute coagulopathy after severe trauma: A multivariate analysis of 1987 patients. Emerg Med J. 2010; 27: 934-939.

Yu TC, Yang FL, Hsu BG, et al.: Deleterious effects of aggressive rapid crystalloid resuscitation on treatment of hyperinflammatory response and lung injury induced by hemorrhage in aging rats. J Surg Res. 2013; 187: 587-595.

Gerth K, Ehring T, Braendle M, et al.: Nitric oxide scavenging by hydroxocobalamin may account for its hemodynamic profile. Clin Toxicol (Phila). 2006; 44(suppl 1): 29-36.

FDA Approves Drug to Treat Cyanide Poisoning: US Food and Drug Administration [serial online]. 2006. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108807.htm. Accessed April 2, 2014.

Bebarta VS, Pitotti RL, Dixon P, et al.: Hydroxocobalamin versus sodium thiosulfate for the treatment of acute cyanide toxicity in a swine (Sus scrofa) model. Ann Emerg Med. 2012; 59: 532-539.

Bebarta VS, Pitotti RL, Dixon PS, et al.: Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest. Ann Emerg Med. 2012; 60: 415-422.

Greenberg SS, Xie J, Zatarain JM, et al.: Hydroxocobalamin (vitamin B12a) prevents and reverses endotoxin-induced hypotension and mortality in rodents: Role of nitric oxide. J Pharmacol Exp Ther. 1995; 273: 257-265.

Bebarta VS, Garrett N, Boudreau S, et al.: A prospective, randomized trial of intravenous hydroxocobalamin versus whole blood transfusion compared to no treatment for Class III hemorrhagic shock resuscitation in a prehospital swine model. Acad Emerg Med. 2015; 22: 321-330.

Butler FK, Holcomb JB, Schreiber MA, et al.: Fluid resuscitation for hemorrhagic shock in tactical combat casualty care: TCCC guidelines change 14-01 - 2 June 2014. J Spec Oper Med. 2014; 14: 13-38.

D’Alleyrand JC, Dutton RP, Pollak AN: Extrapolation of battlefield resuscitative care to the civilian setting. J Surg Orthop Adv. 2010; 19: 62-69.

Dutton RP, Mackenzie CF, Scalea TM: Hypotensive resuscitation during active hemorrhage: Impact on in-hospital mortality. J Trauma. 2002; 52: 1141-1146.

Schreiber MA, Meier EN, Tisherman SA, et al.: A controlled resuscitation strategy is feasible and safe in hypotensive trauma patients: Results of a prospective randomized pilot trial. J Trauma Acute Care Surg. 2015; 78: 687-695.

Frankel DA, Acosta JA, Anjaria DJ, et al.: Physiologic response to hemorrhagic shock depends on rate and means of hemorrhage. J Surg Res. 2007; 143: 276-280.

White JM, Cannon JW, Stannard A, et al.: A porcine model for evaluating the management of noncompressible torso hemorrhage. J Trauma. 2011; 71: S131-S138.

Pamidi PV, DeAbreu M, Kim D, et al.: Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements. Clin Chim Acta. 2009; 401: 63-67.

Rixen D, Siegel JH: Bench-to-bedside review: Oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock. Crit Care. 2005; 9: 441-453.

Guyette F, Suffoletto B, Castillo JL, et al.: Prehospital serum lactate as a predictor of outcomes in trauma patients: A retrospective observational study. J Trauma. 2011; 70: 782-786.

Tobias AZ, Guyette FX, Seymour CW, et al.: Pre-resuscitation lactate and hospital mortality in prehospital patients. Prehosp Emerg Care. 2014; 18: 321-327.

Yamazaki Y, Saito A, Hasegawa K, et al.: Blood lactate concentrations as predictors of outcome in serious hemorrhagic shock patients. Masui. 2006; 55: 699-703.

Hoskins SL, do Nascimento P Jr, Lima RM, et al.: Pharmacokinetics of intraosseous and central venous drug delivery during cardiopulmonary resuscitation. Resuscitation. 2012; 83: 107-112.

Murray DB, Eddleston M, Thomas S, et al.: Rapid and complete bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning in minipigs after intraosseous administration. Ann Emerg Med. 2012; 60: 424-430.

Sampaio AL, Dalli J, Brancaleone V, et al.: Biphasic modulation of NOS expression, protein and nitrite products by hydroxocobalamin underlies its protective effect in endotoxemic shock: Downstream regulation of COX-2, IL-1beta, TNF-alpha, IL-6, and HMGB1 expression. Mediators Inflamm. 2013; 2013: 741804.

Balogh Z, McKinley BA, Cocanour CS, et al.: Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome. Arch Surg. 2003; 138: 637-642. 27. Park PK, Cannon JW, Ye W, et al.: Transfusion strategies and development of acute respiratory distress syndrome in combat casualty care. J Trauma Acute Care Surg. 2013; 75: S238-S246.

Simmons JW, White CE, Eastridge BJ, et al.: Impact of improved combat casualty care on combat wounded undergoing exploratory laparotomy and massive transfusion. J Trauma. 2011; 71: S82-S86.

Sondeen JL, Prince MD, Kheirabadi BS, et al.: Initial resuscitation with plasma and other blood components reduced bleeding compared to hetastarch in anesthetized swine with uncontrolled splenic hemorrhage. Transfusion. 2011; 51: 779-792.

Bulger EM, May S, Kerby JD, et al.: Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: A randomized, placebo controlled trial. Ann Surg. 2011; 253: 431-441.

Alam HB, Punzalan CM, Koustova E, et al.: Hypertonic saline: intraosseous infusion causes myonecrosis in a dehydrated swine model of uncontrolled hemorrhagic shock. J Trauma. 2002; 52: 18-25.

Bebarta VS, Vargas TE, Castaneda M, et al.: Evaluation of extremity tissue and bone injury after intraosseous hypertonic saline infusion in proximal tibia and proximal humerus in adult swine. Prehosp Emerg Care. 2014; 18(4): 505-510.

Ortiz D, Barros M, Yan S, et al.: Resuscitation from hemorrhagic shock using polymerized hemoglobin compared to blood. Am J Emerg Med. 2014; 32(3): 248-255.

Murao Y, Isayama K, Saito F, et al.: Effect of hypertonic saline resuscitation on CD4+CD25 + regulatory T cells and gammadelta T cells after hemorrhagic shock and resuscitation in relation to apoptosis and iNOS. J Trauma. 2009; 67: 975-982.

Moon-Massat P, Scultetus A, Arnaud F, et al.: The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine. Injury. 2012; 43: 638-647.

Garrett N, Bebarta V, Boudreau S, et al.: Intravenous hydroxocobalamin versus Hextend versus control for Class III hemorrhage resuscitation in a prehospital swine model. Mil Med. 2015 (in press).

Riou B, Berdeaux A, Pussard E, et al.: Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs. Intensive Care Med. 1993; 19: 26-32.

Yannopoulos D, Metzger A, McKnite S, et al.: Intrathoracic pressure regulation improves vital organ perfusion pressures in normovolemic and hypovolemic pigs. Resuscitation. 2006; 70: 445-453.

Hannon JP, Bossone CA, Wade CE: Normal physiological values for conscious pigs used in biomedical research. Lab Anim Sci. 1990; 40: 293-298.




DOI: https://doi.org/10.5055/ajdm.2015.0203

Refbacks

  • There are currently no refbacks.