IS EPIDURAL ANAESTHESIA THE MAGIC BULLET TO STAMP OUT SURGICAL INFECTION AND SEPSIS?
Hon. Anesthetist (Retd.) JJ Hospital, Mumbai. Bombay Hospital, Mumbai.
Infection and sepsis are complex phenomenon with dimensions that are real, significant, continuing and changing. Despite continued advances in surgical and anaesthetic skills postoperative infection still remains a formidable problem. The application of germ concept of infection, antiseptic and aseptic techniques, immunization procedures, toxoids, vaccines and general use of antibiotics during the past century have had revolutionary effects but the infection, nevertheless, continues to be the serious problem of worldwide scope.  The concept that bacteria which are ubiquitous in our environment are the cause of infection, led to widespread prophylactic use of antibiotics in surgery. This apparently, not only failed to decrease the incidence of infection but also has contributed to the complexity of the problem through development of infection produced by antibiotic resistant bacteria.  Furthermore, failure of therapy is now often excused by the assumption that the host resistance is impaired. Not surprisingly, many antibiotic chemotherapeutic agents are immunosuppressive.  Despite the development of numerous newer additional antibiotics after the introduction of penicillin, relatively small gains have been made in improving the mortality of patients with the most severe surgical infections namely septic peritonitis and pancreatic abscess.  This suggests that despite the last 50 years of research our attempt to produce the ‘magic bullet’ - a new and perfect antimicrobial agent to control severe infection and sepsis in surgery, have failed.
1. Shock : Pathophysiology the appearance of infection in critically ill patient is of great concern. Tissue hypoxia (shock) is frequently seen in the critically ill. Tissue hypoxia predisposes the critically ill patients to development of infection and multiple organ failure (m.o.f.).  Sepsis and its complications including ARDS, acute renal failure and m.o.f. are frequent causes of death in patients admitted to Critical Care Unit.  Monitoring and therapeutic procedures that breach the physical barriers, which normally protect the organism from invasion by bacteria, viruses and fungi through various catheters are responsible for infection and sepsis in the critically ill who are usually in shock. This was demonstrated in an animal experiment in which the animal was bled to produce shock. The sites where the needles were inserted for infusion, developed infection. 
2. Immunity : It plays a vital role in development and prevention of infection. The increased susceptibility to infection is a well recognised feature of immunosuppression and high dose of steroids especially when patients become neutropenic.  The deterioration of ‘immunoreaction’ happens shortly after trauma, burns, and shock and renders the patient vulnerable to infection.  Studies examining the relationship between the function of macrophage neutrophil, T and B cells and development of infection in critically ill and injured patients have shown that alterations in immune responses precede infection and that increased susceptibility to infection in critically ill and injured patients have shown that alterations in immune responses precede infection and that increased susceptibility to infection is associated with the magnitude of immunologic abnormality. Multiple immunologic abnormalities have been identified after haemorrhage, surgical trauma, burns and shock.  Critically ill patients who are immunosuppressed [6,11] are easily vulnerable to infection and often resistant to the most potent antibiotics.  Many other factors are involved such as stress induced hypersecretion of catecholamines, corticosteroids, hypercatabolism all of which are responsible for immunosuppression and increased susceptibility to infection. 
3. Stress of surgery : The fact that phagocytosis is depressed following surgical stress and reticuloendothelial (RE) function is diminished in shock underlines the importance of stress component of surgery and anaesthesia. It must be emphasised here, that general anaesthesia (GA) is not stress-free because, it does not block the pain conducting sensory path. It only makes the patient unconscious. However, unconsciousness under GA does not prevent neuroendocrine stress reaction to pain stimuli from the site of injury.  This fact is overlooked by many anaesthetists. The possible adverse effects of surgical stress are enumerated in Table 1. Surgical stress in more likely to render the patient to development of infection following surgery under GA. In fact the postoperative infection is the baneful effect of postoperative shock following surgery under GA. Both B and T cell lymphocyte function is depressed by GA and surgery. This suggests that stress component of GA and surgery plays a significant role in development of
TABLE 1 Possible adverse effects of stress [ 12 ] Cardiovascular
Increased heart work
- tissue hypoxia and acidosis Metabolic Increased protein - impaired tissue repair
Hyperglycaemia Reduced insulin secretion (initially)
Sodium and water retention
Increased potassium loss
Increased mobilization and
metabolism of fat
- ? increased risk of thrombus formation
- increased ketone production
Depressed protection against infection and tumour growth
Depressed inflammatory response
Depressed immune response
postoperative infection. 
4. Impaired Tissue Perfusion : However, the most important factor, that is, the relation between the blood flow in wounds and their susceptibility to infection, has received little attention and the host defences are dependent on the antibacterial substances circulating through the contaminated wounds in defence against bacterial invasion. Miles and Niven  showed that shock impairs tissue perfusion and suppresses wound defence mechanism. Aseptic technique or state of the art operation theatres can prevent infection developing in the wounds which have inadequate circulation. The oldest principle in surgery is that the wound with poor perfusion heals poorly and gets infected easily. This poor perfusion is obviously due to shock state resulting in increased viscosity of blood which decreases capillary flow resulting in poor nutrition to tissues and cells, immunosuppression, decreased phagocytic activity, and profused exudation (case 1) in the wound as a result of increased permeability of capillaries following hypoxia. [14,15] Thus, impaired tissue perfusion is the main cause of infection and sepsis.
Treatment of Severe Infection and Sepsis : It is abundantly clear from the evidence presented above, that impaired tissue perfusion is the main cause of infection and sepsis and therefore the ‘hall mark’ for treatment surrounds the maintenance of adequate oxygen and nutrients to tissues and cells along with antibacterial substances to fight germs.  This basic fact is overlooked simply because the concept that bacteria are the cause of infection and sepsis and that antibiotics prevent and cure it. Impaired tissue perfusion is associated with all types of shock. In shock ATP (adenosine triphosphate) production declines leading to dysfunction of cell, tissue and organ. Multiple organ failure that follows involves reticular endothelial system (RE) of which liver is the most important organ. In hepatic failure,  metabolism of all nutrients is deranged. This limits the nutritional support. Protein is central to hepatic regeneration, overall protein synthesis in body economy and repair of tissues. Protein synthesis influences all the important functions in critical illness including host defences and immunological functions.
Role of Epidural Anaesthesia in prevention and treatment of Shock, Infection and Sepsis : Epidural anaesthesia suppresses neuroendocrine reaction induced by burns, trauma, surgery and controls shock. Vasodilation that follows sympathetic block, provides hyperperfusion to tissues and cells. Cells get adequate quantity of nutrients and oxygen to produce ATP, an energy which is essential for cellular function. This restores organ functions. The effect is dramatic as demonstrated by spontaneous breathing, free flow of urine, control of infection and haemodynamic stability in a patient with septic peritonitis who was on ventilator in ICU. A burns wound that was exudating profusely became dry within 24 h. (case 1). Similarly, a patient with septic peritonitis (case 2) felt hungry and asked for food only after 12 h of continuous EA. This suggests that her Gastrointestinal tract function returned to normal along with respiratory, cardiovascular and renal functions. Improved tissue perfusion, after EA improved RE function along with patient resistance to shock, trauma and infection. Similarly, it increased generation of immunoproteins, improved systemic immunity, eliminates infection and increases survival.  This is the most beneficial effect of EA where antibiotics have failed to control infection and sepsis as demonstrated in case 1 and 2.
A 35 year old man was in shock due to severe burns (55% body surface area involving arms, cheek and thighs). He was exudating profusely from the burn surface, despite antibiotics and antishock treatment on the fourth day of admission. After proper consent, EA (a single dose, 10 ml of 0.3% of Bupivacaine hydrochloride) was administered in the second thoracic space to control shock. The patient sat up in bed and gave a smile followed by a miraculous response the next day when his exudating surface was found absolutely dry. In shock microcirculation is affected producing capillary leak. EA produces vasodilation and restores capillary circulation and tissue perfusion.
A 22 year old woman was admitted with septic peritonitis and shock. The pus from the peritoneal cavity was drained per vaginum under EA (10 ml of 0.5 per cent Bupivacaine hydrochloride) administered through a catheter placed in lumbar region. Anaesthesia was continued for 12 h (10 ml of 0.3 per cent Bupivacaine hydrochloride injected at 4 h interval). After 12 h she looked perfectly normal. The shock syndrome had vanished. She was hungry and asked for food which was allowed. This suggests a remarkable recovery from septic shock just after 12 h of EA. Improved tissue perfusion improved GI tract functions along with improvement in functions of other organs of the body. Next day she was operated for hysterectomy. At that time her peritoneal cavity was absolutely clean. No sign of inflammation anywhere. However, postoperative EA was not continued even though she was operated under EA. On the third day of operation she developed septic shock with MOF syndrome which did not respond to intensive therapy given earlier for three days with mechanical ventilation and antibiotics. Therefore EA (10 ml of .3 per cent Bupivacaine hydrochloride) was administered on 6th day of operation. The effect was dramatic. The urine flow resumed promptly along with improvement in haemodynamics, pulmonary insufficiency relieved, infection controlled, metabolic derangement and electrolyte imbalance corrected. EA was continued for 48 h. Sherecovered completely.
DISCUSSION AND CONCLUSION
Impaired tissue perfusion is the main cause of infection and sepsis. Tissue perfusion is impaired in shock following trauma, burns, haemorrhage and postoperative state. Therefore, shock must be treated to improve tissue perfusion and control infection and sepsis. EA is the most effective and rational treatment for shock which produces dramatic effect.
It is the magic bullet. The infected wound after burns, which was exudating profusely despite antibiotics, became dry within 24 h. The drudgery of frequent wound dressing was completely eliminated and the workload of nursing staff is considerably reduced. I fervently appeal to my anaesthetist colleagues to use EA routinely to prevent and treat postoperative and post-traumatic shock, infection and sepsis, particularly in critically ill and open heart surgery. EA should be considered as an integral and essential component of anaesthesia and surgery. Besides, EA has vast therapeutic potential. Under EA heart, lungs, liver, kidneys, RE system and GI tract function better because, of improved tissue perfusion. This helps critically ill and shock patient with sepsis recover faster as demonstrated in case reports.
In this new era of cost containment, it will be necessary to scrutinize carefully the resources utilised for the treatment of severe infection and sepsis with costly antibiotics. Besides, the use of nursing staff, their precious time, laboratory tests, duration of hospitalization and uncertain outcome must all be taken into consideration. EA is the most rational least expensive and dramatic in its effect. Moreover, it does not require sophisticated monitoring devices, nor any laboratory tests. Since the recovery is faster, the patient’s stay in hospital is also greatly shortened. It is my considered opinion that all these benefits justify the use of EA routinely to prevent and treat surgical infection, sepsis and shock.
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