Earning the Anesthetic

Resuscitation is the primary intraoperative role for the anesthesiologist during DCS for the patient with major trauma. Hence, patients “earn an anesthetic” once hemodynamic stability has been achieved. It is imperative for the trauma anesthesiologist to be aware of the patient’s injuries before anesthetic agents are indiscriminately titrated. There may be a significant amount of bleeding into the retro-peritoneum from a severe pelvic injury or bleeding into compartments due to bilateral femur fractures requiring resuscitation in volumes not anticipated. Trauma patients in compensated or decompensated shock have a much lower volume of distribution for all anesthetic agents and these must be adjusted accordingly. If the patient has a positive focused abdominal sonogram for trauma (FAST) exam with a suspected tense peritoneum, high-dose opioid loading should be delayed until surgical hemostasis has been achieved. DCR is carried out in a high blood product ratio-driven manner while maintaining systolic blood pressure greater than 90 mmHg systolic or a mean arterial pressure of greater than 50 mmHg in the patient without TBI [31•, 32]. In patients who remain severely hypotensive during DCR, there may not be an opportunity to administer any additional anesthetic agents.

Induction and maintenance of anesthesia may produce profound hypotension and/or cardiac arrest in major trauma, and anesthesiologists should be familiar with alternative amnestic agents. Both induction agents and volatile anesthetics have a dose-dependent negative effect on hemodynamic stability due to vasodilation. Thus, it may be challenging for the anesthesiologist to provide amnesia for victims of major trauma. Awareness is a rare complication during general anesthesia with a reported prevalence of 0.1–0.2 % in adults undergoing elective surgery, but the prevalence is higher in major trauma cases when the patient is too hemodynamically unstable to tolerate anesthesia [33, 34] Patients who experience awareness under anesthesia may develop serious long-term consequences such as PTSD [35].

Benzodiazepines are a class of drugs that provide amnesia but do not cause vasodilation, and thus can be used in hemodynamically unstable patients. These agents can reduce the incidence of awareness during resuscitation until additional anesthesia can be given [34]. Scopolamine, an anticholinergic amnestic, has historically been touted as an effective agent to prevent intraoperative awareness, although data regarding the dosing and effectiveness in trauma are sparse [36]. Based on a 2006 Practice Advisory, either benzodiazepines or scopolamine may be considered on a case-by-case basis for selected patients, including trauma patients who may require smaller doses of anesthetics [37]. Our institutional practice is to administer intravenous midazolam (2–4 mg) or diazepam (5–10 mg) if the patient is too unstable to tolerate volatile anesthetics and deemed to be at risk for intraoperative awareness. An anecdotally endorsed dose for intravenous scopolamine is a single administration of 0.2 mg. Scopolamine must be used with caution in patients with TBI because this agent has a long half-life (4.5 h) and can confound subsequent neurological examinations (i.e., pupillary dilatation).

Volatile Anesthetics: Effects in the Trauma Patient

Volatile anesthetics such as desflurane, isoflurane, and sevoflurane have been identified as effective modulators of the inflammatory response in various states of tissue injury, exerting beneficial effects on organ function and overall outcome in both animal [38–41] and human models [42–44] Most previous studies elucidating the protective potential of volatile anesthetics have focused on ischemia–reperfusion injury and biomarkers of organ injury rather than clinical outcomes [45]. Although volatile anesthetics are often used as anesthetic agents during the initial anesthesia for surgery for major trauma, the effect of these agents on the inflammatory response, coagulation system, and outcomes of trauma patients is unknown. At our institution, as blood pressure improves to greater than 90 mmHg systolic, inhalation agents are increased to half minimum alveolar concentration (MAC) or greater. In patients with severe TBI, volatiles are normally titrated to less than 1 MAC to avoid dose dependent increases in CBF and ICP. Vigilance when administering volatile anesthetics is imperative because the patient’s clinical condition may rapidly change, especially if missed injuries are encountered during or after DCR and DCS. There are no quality data to support preferential selection of one volatile agent over others in trauma patients. In patients with multiple injuries and multiple episodes of severe hemodynamic instability, volatile agents with lower blood-gas partition coefficients are generally selected (i.e., sevoflurane or desflurane) to permit rapid titration. At our institution, we generally avoid nitrous oxide in trauma patients for several reasons. First, nitrous oxide expands all gas spaces and can worsen pneumothoraces, pneumocephalus, small bowel obstructions, and expand endotracheal tube cuffs. Second, nitrous decreases hypoxic drive, increases pulmonary vascular resistance, and can cause diffusion hypoxia [46, 47]. In patients with TBI, nitrous oxide increases CMRO 2 and ICP and may disturb cerebral blood flow-CMRO 2 coupling [46]. Finally, there is evidence that nitrous may alter immunological responses to infection, cause apoptosis, increase homocysteine levels, and mask myocardial depression [47, 48] (Fig. 1).

Fig. 1 Overview of anesthetic considerations during damage control resuscitation (DCR) and damage control surgery (DCS) [64•, 65•] Full size image

Titration of High-Dose Opioids

The return of adequate micro-circulatory flow is the ultimate goal of trauma resuscitation [49]. After the control of acute hemorrhage, ongoing resuscitation continues using warmed blood components administered at high ratios with correction of electrolytes [50]. The correction of acid–base derangements is accomplished with adequate resuscitation and not pharmacologic correction (i.e., sodium bicarbonate [51] and vasopressors). The result of this continued resuscitation is an increasing systolic blood pressure. An increase in systolic blood pressure is an indicator of increasing macro-circulatory pressure, but this does not necessarily indicate an increase in macro or micro-circulatory flow. As the blood pressure continues to rise, fentanyl may be added to the anesthetic regimen in order to begin dilating the microcirculation. In our practice, we begin with 50–150 mcg doses of intravenous fentanyl and observe the physiologic response. If there is a reduction in blood pressure, the resuscitation is continued until there is a positive response with return of blood pressure to the systolic target (>90 mmHg). Hypotension following increased MAC or doses of opioid may be an indication of a reduction in vascular tone. As this response becomes minimal with subsequent doses of fentanyl, the dose is increased in a stepwise fashion. This dose-response is continued until the patient tolerates a single bolus of approximately 250 mcg of fentanyl. In most cases the patient will receive a total dose of 20–30 mcg per kilogram or more of fentanyl. It must be remembered that the patient’s estimated blood volume is constantly changing during the resuscitation, as is the plasma level of the dosed opioid. The dose is ultimately determined by the physiologic response of the patient following administration of the opioid and titration of other anesthetic agents.

If there is no longer a response to fentanyl while goal-directed resuscitation continues, and there is still evidence of tissue hypoperfusion as evidenced by an elevated lactate and base deficit, our institutional practice is to add an additional opioid such as intravenous methadone in 10 mg increments to a maximum dose of 20–30 mg if the patients QTc is within normal limits (<440 ms). The addition of methadone causes additional vasodilatation and may require additional resuscitation. This high-dose opioid-resuscitation method can only be carried out if the patient’s perfusion pressure is adequate and hemorrhage control assured. The addition of methadone may help blunt the catecholamine response until arrival at the intensive care unit or radiology suite. When methadone is contraindicated, an alternative opioid for titration is hydromorphone, titrated in 0.2–0.4 mg increments to a total dose of 2 or more mg for the case. Morphine is generally avoided in our practice due to concerns about histamine release, which may exacerbate hypotension.

It must be noted that this high-dose opioid anesthetic technique has not been previously described with such detail in the literature, but has been the mainstay of the anesthetic technique combined with intraoperative resuscitation at the R Adams Cowley Shock Trauma center for many years. Trauma anesthesiologists at our institution have speculated that administration of high doses of opioids may improve tissue perfusion [52•], though in vivo evidence to support this theory is lacking. Opioids may blunt deleterious activation of the sympathetic nervous system and alter microcirculation in a way that may prevent further tissue damage in hemorrhagic shock. It has been shown that high levels of catecholamines are associated with an increase in biomarkers that indicate endothelial damage, glycocalyx breakdown [53] and perpetuation of hyper fibrinolysis [53, 54]. Biomarkers related to ongoing catecholamine release are also related to coagulopathy, which increases mortality [55, 56]. Restoration of adequate micro-circulatory blood flow is crucial in shock reversal, as well as protection of the endothelial glycocalyx. This is essential in order to minimize leukocyte-endothelial interaction, as well as maintaining the integrity of the vascular basement membrane [49, 57•]. As the lactate and base deficit normalize and the vasodilatory response to the opioid becomes minimal, two central, but unequivocally essential resuscitation goals are achieved: return of micro-circulatory flow and the correction of the acute coagulopathy of trauma, and blunting of the catecholamine response.

Several studies have documented the beneficial role of opioid receptor agonists in hemorrhagic shock [52•, 58, 60]. In various animal studies, opioids have been shown to precondition skeletal and myocardial tissue, [58, 59] promote hemodynamic recovery [62], and provide protection against acute ischemia [61]. Morphine has been shown to attenuate microvascular hyperpermeability after hemorrhagic shock, possibly due to dependence on protein kinase A [62]. Retrospective studies are planned using data from the recently completed pragmatic randomized optimal platelet and plasma ratios (PROPPR) [63] to help elucidate the impact of opioid dosing on the inflammatory response and coagulation abnormalities in patients with severe trauma who require massive transfusion. Further prospective in vivo investigations are indicated to establish the mechanism, physiological effects, and outcomes associated with a high-dose opioid anesthetic approach for patients with major trauma.