Alcohol Abuse and the Injured Host

Abstract

Traumatic injury ranks as the number one cause of death for the under 44 year old age group and 5th leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the post-resuscitation period, particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury; with intoxicating blood alcohol levels present in more than 40% of injured patients (1–5). Severity of trauma, hemorrhagic shock and injury is higher in intoxicated individuals than that of sober victims, resulting in higher mortality rates in this patient population. Necessary invasive procedures (surgery, anesthesia) and subsequent challenges (infection) that intoxicated trauma victims are frequently subjected to are additional stresses to an already compromised inflammatory and neuroendocrine milieu and further contribute to their morbidity and mortality. Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis following injury.

Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock

“…Our lab and others have reported the increased level of plasma cytokines immediately after HI (34, 49). Some of these cytokines begin to appear as early as one hour after HI (34, 38, 50, 51). The initial inflammatory response is likely to be a repair process to balance cellular homeostasis, but persistent exacerbated inflammation following the initial insult contributes to organ dysfunction (5, 52, 53).…”

Acute immunomodulatory effects of binge alcohol ingestion

“…Acute alcohol exposure was encountered in more than 30% of trauma patients and intoxication carried the highest risk for injury (Afshar et al, 2014; Gmel et al, 2006). In preclinical trauma studies, alcohol-induced vasodilation, diuresis, decreased cardiac output, impaired vasoreactivity, and depressed myocardial contractility negatively impacted resuscitation and worsened outcomes (Molina, Sulzer, & Whitaker, 2013). Alcohol-exposed trauma victims who survived their injuries were at increased risk for nosocomial infection and acute respiratory distress syndrome (Afshar et al, 2014; Gmel et al, 2006).…”

“…Experimental studies have shown acute alcohol exposure resulted in suppressed pro-inflammatory cytokine release in response to an inflammatory challenge, decreased neutrophil recruitment and phagocytic function, and impaired chemotaxis (Molina et al, 2013). Most murine models focused on time points when blood alcohol was no longer present (Fuance, Gregory, & Kovacs, 1997, 1998), but even in murine models examining very early effects on immune response when blood alcohol was still present, markedly suppressed cellular immunity with inhibition of IL-6 and TNF-α production was found (Goral, Choudhry, & Kovacs, 2004; Goral & Kovacs, 2005).…”

Heavy Ethanol Intoxication Increases Proinflammatory Cytokines and Aggravates Hemorrhagic Shock-Induced Organ Damage in Rats

“…Acute alcohol intoxication is a significant risk factor for traumatic injury and causes higher morbidity or mortality rates in patients with HS [6, 7]. Acute alcohol intoxication is a clinically harmful condition that commonly follows the ingestion of a large amount of alcohol [8].…”