Ketamine-based total intravenous anesthesia versus isoflurane anesthesia in a swine model of hemorrhagic shock.
BACKGROUND
Inhalational anesthetics can cause profound hemodynamic effects including decreases in systemic vascular resistance and cardiac inotropy. Although widely used in uncontrolled hemorrhagic shock (UHS), their consequences compared with other anesthetic regimens are not well-studied. Ketamine-based total intravenous anesthesia (TIVA) may produce less profound cardiovascular depression, and has been used during elective surgery but rarely during traumatic shock. The purpose of this study was to compare the effects of isoflurane (ISO) and TIVA regimens in a swine grade V liver injury model. We hypothesized that TIVA would result in less hypotension and dysfunctional inflammation than ISO.


METHODS
Twenty swine were randomized blindly to receive either 1% to 3% ISO, or intravenous ketamine, midazolam, and buprenorphine for maintenance anesthesia. Six animals acted as controls. After sedation and intubation, randomized anesthesia was initiated and monitored by an independent animal technician. Invasive lines were placed followed by celiotomy and splenectomy. Baseline mean arterial pressure (MAP) was documented and a grade V liver injury created. After 30 minutes of UHS, animals were resuscitated with 8 mL of Ringer's lactate per milliliter blood loss at 165 mL/min. MAP and tissue oxygen saturation (StO2) were continuously recorded. The animals were sacrificed 120 minutes after injury and lung tissue was harvested. Serum cytokines (interleukin-6 [IL-6], IL-8, and tumor necrosis factor-alpha [TNF-alpha]) were quantified with enzyme-linked immunosorbent assay. Lung cytokine mRNA levels were quantified with real time reverse transcriptase polymerase chain reaction.


RESULTS
Animal weight, liver injury pattern, and blood loss were similar (p > 0.1). The ISO group had a lower MAP at baseline (p = 0.02), at injury (p = 0.004), and study completion (p = 0.001). After resuscitation, MAP decreased in the ISO group but remained stable in the TIVA group. StO2 was significantly higher in the TIVA group immediately after injury (p = 0.004), but similar between groups throughout the remainder of the study. Animals who received TIVA trended toward higher levels of lactate and lower pH throughout the study, reaching significance at 30 minutes postinjury (p = 0.037 and 0.043). Inflammatory cytokine (IL-6, IL-8, and TNF-alpha) production did not differ between groups, however TNF-alpha mRNA production was significantly lower in the TIVA group (p = 0.04).


CONCLUSIONS
Although a TIVA regimen produced less pronounced hypotension in a swine model of UHS than did ISO, end-organ perfusion with TIVA appeared to be equivalent or inferior to ISO. In circumstances of limited resources, such as those experienced by forward Army surgical teams, a ketamine-based TIVA regimen may be an option for use in UHS.
Section of Trauma and Surgical Critical Care, Department of Surgery, Oregon Health & Science University, Portland, Oregon 97239, USA.
Michael S
MS
Englehart
Carrie E
CE
Allison
Brandon H
BH
Tieu
Laszlo N
LN
Kiraly
Samantha A
SA
Underwood
Patrick J
PJ
Muller
Jerome A
JA
Differding
Rebecca S
RS
Sawai
Ayhan
A
Karahan
Martin A
MA
Schreiber
D000771:Anesthesia, Intravenous; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000502:physiology; D011897:Random Allocation; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D007530:Isoflurane