Thoracic epidural block in sepsis: Looking beyond the known.

Thoracic epidural block (TEB) is a commonly used anesthetic technique, indicated for its well-established analgesic as well as nonanalgesic effects.[1] Previously documented nonanalgesic benefits include enhanced gastrointestinal motility that in turn reduces the duration of hospital stay and hence the hospital cost, reduced intraoperative blood loss, and an attenuated perioperative stress response.

The use of TEB in patients with sepsis has traditionally been considered a relative contraindication.[2] There is evidence however, to suggest that TEB may indeed have a beneficial role during sepsis, offering a new paradigm for its application.[3]

It is well established that sepsis is characterized by splanchnic hypoperfusion and redistribution of blood flow away from the mucosa of gut. This leads to disruption of mucosal barrier and consequent translocation of bacteria across the gut wall, heralding sepsis.[3] TEB results in a sympathetic blockade, and if this extends to the neural supply of splanchnic circulation intestinal blood flow may increase thus attenuating sepsis.

To extend this hypothesized benefit of TEB during sepsis, evidence should convince us of two individual effects. First, that TEB increases splanchnic blood flow, and second that it improves outcome in patients with sepsis.

Regarding the first effect, that TEB can indeed augment the splanchnic blood flow is well documented in aseptic experimental models,[45] aseptic patients undergoing abdominal surgery,[678] and experimental septic models as well.[91011] Herein, the augmentation in splanchnic blood flow by TEB was documented using various methods such as intravital microscopy,[451011] laser Doppler flowmetry,[8] fluorescent microsphere reference withdrawal technique[9] and intramucosal pH.[67]

Besides an increase in splanchnic circulation, there are suggestions of other mechanisms by which TEB may benefit during sepsis. TEB was also seen to produce advantageous effects in experimental models of adverse pathophysiological situations that simulate changes of a septic state.[1213] Herein, in an experimental model of mesenteric ischemia, TEB attenuated the systemic inflammatory response and intestinal damage evidenced by levels of antioxidants, superoxide dismutase, glutathione peroxidase, myeloperoxidase, malondialdehyde, intracellular adhesion molecule-1, etc.[13] In another experimental model of hypoxic hypoxia, use of TEB prevented gut injury and subsequent translocation of endotoxin.[12]

Based on the above discussion, there is thus substantial evidence to suggest the potential for the benefit of TEB in attenuating the progression of sepsis.

However, when it comes to evidence of the second effect of TEB during sepsis, namely, improved outcome in septic patients, there is a relative paucity of literature. The clinical application of TEB for exploiting the suggested benefits in sepsis is perhaps limited by a fear of infective complications and hemodynamic perturbations.

Only three published clinical studies dealing with the potential benefits of TEB in patients with sepsis could be located.[141516] The earliest was conducted by Spackman et al.[14] in critically ill patients with peritonitis and adynamic bowel following abdominal surgery. In their double-blinded, randomized, and controlled study, the effect of TEB versus intravenous morphine was assessed on gastric perfusion and motility evidenced by gastric tonometry and abdominal ultrasound, in addition to paracetamol absorption. The gastric perfusion was found to be significantly better with the use of the epidural, the intramucosal pH being significantly higher and mucosal: arterial PCO2 gradient being lower in patients with the blockade (P = 0.024). Significant improvements were seen in the ultrasound appearance of the small bowel as well (P = 0.004). It was concluded that the epidural analgesia resulted in improvements in gastric mucosal perfusion and ultrasound appearance of the small bowel, indicating its potential clinical benefit in a patient population in which it is traditionally contraindicated! Another randomized clinical trial[15] evaluated whether combining TEB along with general anesthesia could decrease the sepsis-related postoperative mortality and morbidity. This randomized controlled study included adult patients undergoing emergency laparotomy for small intestinal perforation peritonitis-induced sepsis. The use of perioperative TEB decreased the postoperative mortality and major systemic morbidity, though the improvements were statistically insignificant. There was a significantly earlier return of bowel motility and earlier discharge from the hospital. Recently, a trial extended the previous work of evaluating the role of TEB in patients with perforation peritonitis undergoing abdominal laparotomy further.[16] Herein, systemic inflammatory markers of sepsis were also evaluated in addition to clinical outcome predictors. The inflammatory markers included interleukin (IL)-6, IL-10, procalcitonin, and C-reactive protein. TEB was associated with a statistically insignificant trend of preservation of anti-inflammatory response (higher IL-10) and lack of alteration of pro-inflammatory reaction (IL-6 levels), along with appreciably lower procalcitonin, and decreased the incidence of raised C-reactive protein. The postoperative sepsis-related organ failure assessment score was also clinically lower with the use of the epidural. The postoperative return of bowel motility was significantly faster.

These clinical studies thus suggest trends of improvement in sepsis-related morbidity, mortality, and inflammatory markers. To conclusively prove the statistical significance of these results, further much larger trials would be required in this hitherto unexplored area.

In this context, it is also relevant to note that in clinical practice it is common to encounter usage of an epidural during “high-risk” laparotomies in patients including those with perforation peritonitis. The reasons however mostly involve analgesia or sparing of anesthetics intraoperatively, or enhanced postoperative bowel motility.

The two primary concerns with the use of thoracic epidural in septic patients, hemodynamic instability, and infective neurological complications also need to be addressed.

It can be hypothesized that hemodynamic instability following the blockade is worse than in an aseptic patient, and hence, the proposed advantage of augmenting gastrointestinal blood flow could be lost. There is some evidence to lay these apprehensions to rest. The use of vasopressor infusion was seen to be similar with or without thoracic epidural in septic patients.[1516] The hemodynamic stability after the block was maintained using fluids and ephedrine boluses as done in routine practice.[16] Studies on endotoxemic animal models have also shown that there is no impairment of hemodynamics following segmental TEB with 0.1% bupivacaine beyond the changes caused by sepsis per se.[1718] Of course, maintenance of blood pressure after the epidural block using fluids and vasopressor boluses must continue to be a clinical goal as in the routine application of the technique. Regarding the apprehension of infective neurological complications when employing the block in septic patients, its rarity (<1%) requires a very large sized clinical trial to address the issue conclusively. None of the clinical trials, however, evaluating TEB in patients with sepsis have observed infective neuraxial complication.[151617] Avoiding long duration of catheterization, use of antibiotics and the removal of the infective focus were cited as probable protective influence against the infective complications.

The patients with sepsis wherein the benefits of TEB on the progression of the disease could be thought about are likely to be a limited subset of septic patients. Preexisting hemodynamic instability and coagulopathy being absolute contraindications to neuraxial block would exclude those with the advanced and severe disease. Furthermore, it needs to be emphasized that the potential benefits of TEB in increasing splanchnic circulation and thus the progression of sepsis, will be applicable only if the sympathetic block extends from T5 to T10,[3] keeping in mind its neural innervation. Lumbar epidural cannot replace the segmental TEB under these circumstances since it would rather offset the benefits, by the unrestricted larger dermatomal spread leading to extensive vasodilation and fall in splanchnic perfusion.[3]

Thus, although epidural catheterization is traditionally avoided in patients with sepsis for fear of infectious complications and lack of any specific benefit, recent animal and clinical data force reconsideration of the latter belief. There has been increasing interest in the use of TEB in sepsis and critically ill patients. Not only is there evidence that TEB increases the gastrointestinal blood flow in sepsis, thus preventing splanchnic ischemia, it may also benefit by attenuating ischemia- or infection-related inflammatory responses originating from splanchnic region by other mechanisms.

Sepsis has continued to be a leading killer, and there are very few interventions such as antibiotic therapy that can actually alter the outcome. This encourages the search for newer interventions or application of known ones beyond their previously established effects. This definitely leaves room for further research and clinical application of using TEB in patients with “sepsis,” with utmost care.