The physiological role of adjuvant hyperbaric oxygen therapy in trauma management and rehabilitation

Transcription

1 The physiological role of adjuvant hyperbaric oxygen therapy in trauma management A systematic review of the literature comparing the therapeutic uses of hyperbaric oxygen therapy in trauma beyond its original clinical application Introduction Major trauma is a devastating health problem, accounting for 20,000 hospital admissions and 5,400 deaths in England alone 1. Mortality and morbidity mainly result from diminished perfusion caused by damaged vasculature, and increased cellular oxygen demand 2 which combine to create severe oxygen debt. The resultant hypoxia presents a major difficulty in trauma management, where the reductions of these effects are a priority. Pathophysiology of trauma Direct trauma to vasculature and lymphatics cause fluid accumulation in the interstitium. Inflammatory pathways activated by the traumatic insult increase capillary permeability, causing vasogenic oedema in the interstitial space 3. With the expanding fluid, interstitial pressure rises, compressing low pressure venous outflow, accentuating further oedema. Vasogenic oedema increases cellular oxygen diffusion distances, compromising perfusion and creating localised oedematous hypoxia. Significant hypoxia causes depletion of aerobically dependent ATP stores (see figure 1). The absence of ATP causes intracellular sodium pumps to fail resulting in intracellular sodium build-up with accompanying potassium and chloride influx. The additional osmotic Figure 1. Illustration of sodium potassium pump biologymad.com/cell.htm The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 1 P a g e

2 pressure this causes increases cytogenic oedema and creates a vicious cycle of oedematous hypoxia on already ischaemic tissue 4. Hyperbaric oxygenation Definition Hyperbaric oxygenation (HBO 2 T) occurs when the patient breathes in 100% oxygen (O2) at pressures exceeding that of the atmosphere 3. High concentration oxygen at atmospheric level, and localised exposure of affected limbs to oxygen does not qualify as hyperbaric oxygenation, so are excluded in this review. Physiological rationale for HBO 2 T action HBO 2 T promotes the reversal of the pathophysiology of trauma via the following mechanisms: i. Increased oxygen diffusion 5 The distance of oxygen diffusion through fluid is proportional to the square root of oxygen concentration in the capillary. At 2 times the atmospheric pressure (2 ATA), the diffusion distance oxygen can accomplish is trebled. The physiological relevance is that oedematous hypoxic tissues can receive oxygen at diffusion distances greater than normobaric oxygenation. ii. Vasoconstriction 6 High partial pressures of oxygen exceeding 500 mmhg causes vasoconstriction, mainly of the arteries, increasing venous outflow relative to arterial inflow. This decreases capillary transudation into the interstitium, and so decreases oedema. There is also an approximate 20% decrease in limb blood loss, with the decreased blood supply offset by increased oxygen tension. iii. Enhanced cellular function 7 Hyperoxia promotes angiogenesis and stimulates fibroblast and collagen synthesis, enhancing healing. HBO 2 T therapy has also been shown to enhance aerobic leucocyte activity, which reduces the common complication of infection in trauma. Current and future indications The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 2 P a g e

3 The current indications for HBO 2 T use are under constant review by the Undersea and Hyperbaric Medical Society (UHMS) as new evidence emerges for future indications. Its current recommended uses as of UHMS 2011 indications for hyperbaric use Compression sickness Carbon monoxide poisoning Air or gas embolism Idiopathic sudden sensorineural hearing loss Crush injury Compartment syndrome Gas gangrene Thermal burns Healing of problematic wounds and compromised skin grafts and flaps Acute blood loss Necrotising soft tissue infection Refractory osteomyelitis Radiation injury (soft tissue and bony necrosis) Box 1 UHMS, are shown in Box 1. This review will focus on the following recommended indications: Compartment syndrome, thermal burns, acute blood loss, fracture healing and traumatic brain injury. Methodology Preliminary reading and discussion of the subject was conducted at the Hyperbaric Medical Facility, Isle of Man 9 (IOM) and the Keyll Darree Medical Library at Nobles Hospital, IOM. The review was conducted through the University of Liverpool website using Scopus, PubMed and Discover archives. Randomised controlled studies were preferred and where unavailable, nonrandomised controlled, observational and case report studies were included. Rationale, review of clinical evidence and discussion for adjuvant HBO 2 T in trauma Compartment syndrome Following trauma, pressures in skeletal muscles may rise sufficiently to cause vascular stasis, resulting in oedematous hypoxia and ischaemia. If interstitial pressure rise over The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 3 P a g e

4 30mmHg, a Fasciotomy is performed to relieve pressure and restore tissue perfusion 10. HBO 2 T is therefore physiologically indicated due to its anti-oedematous and hyperoxygenative properties. Prompt HBO 2 T therapy being effectively used to control post-surgical intracompartmental calf pressures exceeding 35 mmhg 11 ; this effect was also noted despite intra-operative hypotension also being reported, suggesting, although an isolated event, that HBO 2 T therapy may be effective in sub-adequate blood flow. A further case series 12 identified 10 patients who recovered with Fasciotomies following symptomatic compartment syndrome from compartment pressures ranging between mmhg. It is not suggested by the UHMS that HBO 2 T should replace fasciotomy is clinically established cases. However if HBO 2 T is used prophylactically, in situations where compartment syndrome is a risk, such as surgery, it may reduce the incidence of postoperative compartment syndrome. As yet no trials have been conducted into this clinical indication, but this suggests a direction for future research. Thermal burns Burns activate the inflammatory cascade, causing vasodilation and increased vascular permeability. This fluid shift from intravascular to extravascular spaces causes hypovolaemia and localised oedema. It is therefore an indication to use HBO 2 T,due to its vasoconstrictive and antioedematous actions. A retrospective study 13 found that the length of hospital stay in 16 patients with between 18-39% burns was significantly reduced from 33 days in the control group (n=8) to 21 days in the adjuvant HBO 2 T group (n=8) (p=0.05). 24 patients with 40-80% burns receiving adjuvant HBO 2 T therapy required half the number of operations (4 vs 8) compared to those receiving only the standard treatment 14. The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 4 P a g e

5 While these results are encouraging, unless HBO 2 T services become incorporated in burns centres, the risk of moving critically ill patients from major burns units, where their clinical need is greatest, to hyperbaric chambers is likely to be too great. Haemorrhage Managing blood loss remains the foremost challenge in trauma. Decreasing blood stocks, autoimmune rejection and disease transmission risk creates a need for alternatives. The hyperoxygenating and vasoconstrictive effect of HBO 2 T as a temporalising measure for hypoxic tissue is an interesting direction. A randomised controlled trial 15 of HBO 2 T use on 41 patients with haemoglobin levels <90 g/l found that 30% increased their levels of hepatic venous oxygen saturation (ShvO2). Serum lactate levels were also significantly decreased, which reflects decreased anaerobic respiration. These results are encouraging, and suggest that HBO 2 T could be used as an adjuvant to minimise blood transfusions, or even replace transfusions in non-critical scenarios of blood loss. However until facilities are in place to safely treat actively haemorrhaging patients in hyperbaric chambers, blood transfusions will still be favoured. Fractures The treatment of fractures centres on re-establishing the structural integrity of bone, and restoring function to the traumatised area. Fracture healing is impaired by poor vascularity, infection and loss of soft tissues 18. As already discussed, the potential for HBO 2 T therapy in promoting angiogenesis, enhancing leukocyte function and promoting soft tissue repair makes it an interesting adjuvant therapy for fractures. There a paucity of clinical trials carried out on humans with HBO 2 T in fractures. A recent study has found an increased production of bone morphogenic cytokines involved in fracture healing 19, which is encouraging. While these trials suggest potential in HBO 2 T The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 5 P a g e

6 therapy, the lack of randomised trials conducted on humans is limiting. There are currently three ongoing randomised controlled trials to investigate HBO 2 T therapy in fracture healing. Until these are complete, there is insufficient clinical evidence to support or disprove the treatment of fractures with HBO 2 T. Figure CBF - Cerebral brain function, HBOT Hyperbaric Oxygen Therapy Traumatic brain injury The brain consumes 20% of total systemic oxygen, and, due to few energy reserves, is dependent on a good oxygen and glucose supply. It is therefore most vulnerable to hypoxia secondary to a traumatic brain injury (TBI). While no effective treatment for TBI exist, managing secondary brain injury is essential to reducing mortality and morbidity. Secondary injury involves tissue hypoxia, inflammation and resulting cerebral oedema. HBO 2 T has been shown to be effective in high altitude cerebral oedema 24, and the ability of HBO 2 T to correct tissue hypoxia, inflammation and therefore cerebral oedema makes it an interesting and exciting adjuvant therapy for prevention of secondary TBI. These studies demonstrate the impact HBO2 therapy can have on reducing mortality and morbidity. Going forward, a recent trial 27 has demonstrated HBO 2 T inducing significant brain function improvements, as seen in Figure 2, in 56 patients following mild TBI. Side-effects and contraindications of HBO 2 T The side effect profile of HBO 2 T means it should not be treated as completely benign. The most common complications are middle ear barotrauma due to fluctuating atmospheric pressure. Cerebral oxygen toxicity is a rare (incidence due to HBO 2 T are The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 6 P a g e

7 1.3/10,000) but potentially serious complication. However, if rates of decompression are prolonged and strictly controlled, then this risk can almost be reduced to almost zero 28. The only absolute contraindication is an untreated pneumothorax. Where there is polytrauma, particularly including the chest, pneumothorax must be ruled out or treated before HBO 2 T. If a chest drain is correctly inserted, the risk is reduced to almost zero 28. Conclusion and areas for future research The evidence for adjuvant HBO 2 T is compelling at this early stage, suggesting it has a future role in trauma management. This review makes no attempt to specify ideal timings or pressures for treating the individual traumatic insults discussed. In the studies, the specific pressures either were not recorded or conflicted between studies, so few inferences of optimal hyperbaric regimen could not be discerned. This is an essential direction for future research, as the diverse clinical indications may have differing optimal pressures. The review does not apply any economic evaluation to HBO 2 T. Any future research into efficacy and cost effectiveness are essential in assessing HBO 2 T viability. Further information regarding HBO 2 T in the UK is available from the British Hyperbaric Association at The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 7 P a g e

8 Bibliography 1. Bozzette A, Aeron-Thomas A. Reducing trauma deaths in the UK. Lancet 2013;382(9888): Mathieu D. Role of hyperbaric oxygen therapy in the management of lower extremity wounds. Int J Low Extrem Wounds 2006;5(4): Buettner MF, Wolkenhauer D. Hyperbaric oxygen therapy in the treatment of open fractures and crush injuries. Emerg Med Clin North Am 2007;25(1): Myers RA. Hyperbaric oxygen therapy for trauma: crush injury, compartment syndrome, and other acute traumatic peripheral ischemias. Int Anesthesiol Clin 2000;38(1): JYS B. Hyperbaric oxygen therapy in reimplantation of severed limbs: A report of 34 cases. Proceedings of the eighth international conference on hyperbaric medicine 1987: Hills BA. A role for oxygen-induced osmosis in hyperbaric oxygen therapy. Med Hypotheses 1999;52(3): Rowe K. Hyperbaric oxygen therapy: what is the case for its use? J Wound Care 2001;10(4): Society UaHM. Indications for Hyperbaric Oxygen therapy (accessed 01/04/2014). 9. STB W. The role of hyperbaric oxygen therapy in trauma. Trauma 2010;12: Masquelet AC. Acute compartment syndrome of the leg: pressure measurement and fasciotomy. Orthop Traumatol Surg Res 2010;96(8): Van Poucke S, Leenders T, Saldien V, Verstreken J, Beaucourt L, Adriaensen H. Hyperbaric oxygen (HBO) as useful, adjunctive therapeutic modality in compartment syndrome. Acta Chir Belg 2001;101(2): al HGe. Hyperbaric oxygen and skeletal muscle compartment syndrome. Contemporary Orthopaedics 1989;18: The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 8 P a g e

9 13. Cianci P, Lueders HW, Lee H, Shapiro RL, Sexton J, Williams C, et al. Adjunctive hyperbaric oxygen therapy reduces length of hospitalization in thermal burns. J Burn Care Rehabil 1989;10(5): Cianci P LH, Lee H et al. Adjuvant hyperbaric oxygen reduces the need for surgery in 40-80% burns. Journal of Hyperbaric Medicine 1988;3: Ueno S, Sakoda M, Kurahara H, Iino S, Minami K, Ando K, et al. Safety and efficacy of early postoperative hyperbaric oxygen therapy with restriction of transfusions in patients with HCC who have undergone partial hepatectomy. Langenbecks Arch Surg 2011;396(1): Wright JK, Ehler W, McGlasson DL, Thompson W. Facilitation of recovery from acute blood loss with hyperbaric oxygen. Arch Surg 2002;137(7): Necas E, Neuwirt J. Response of erythropoiesis to blood loss in hyperbaric air. Am J Physiol 1969;216(4): Fong K, Truong V, Foote CJ, Petrisor B, Williams D, Ristevski B, et al. Predictors of nonunion and reoperation in patients with fractures of the tibia: an observational study. BMC Musculoskelet Disord 2013;14: Barth E, Sullivan T, Berg E. Animal model for evaluating bone repair with and without adjunctive hyperbaric oxygen therapy (HBO): comparing dose schedules. J Invest Surg 1990;3(4): Ueng SW, Lee SS, Lin SS, Wang CR, Liu SJ, Yang HF, et al. Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits. J Trauma 1998;44(4): IL M. NCT Does hyperbaric oxygen reduce complications and improve outcomes after open tibial fractures with severe soft tissue injury? An interntional multi-centre randomized comtrolled trial. Hyperbaric Service, Alfred Hospital, Melbourne, Australia; Knobe M MS. NCT Hyperbaric oxygen therapy in calcaneal fractures: Can it decrease the soft-tissue complication rate? (HOCIF). Department of Orthopaedic Trauma, RWTH Aachen University, Aachen, Germany; The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 9 P a g e

10 23. M K. NCT Hyperbaric oxygen therapy in distal radius fractures: Can it shorten recovery time and increase fracture healing? (HBOTRadius). Department of Orthopedic Trauma, Aachen University, Aachen, Germany; Hackett PH, Roach RC. High altitude cerebral edema. High Alt Med Biol 2004;5(2): Golden Z, Golden CJ, Neubauer RA. Improving neuropsychological function after chronic brain injury with hyperbaric oxygen. Disabil Rehabil 2006;28(22): Golden ZL, Neubauer R, Golden CJ, Greene L, Marsh J, Mleko A. Improvement in cerebral metabolism in chronic brain injury after hyperbaric oxygen therapy. Int J Neurosci 2002;112(2): Ren H, Wang W, Ge Z. Glasgow Coma Scale, brain electric activity mapping and Glasgow Outcome Scale after hyperbaric oxygen treatment of severe brain injury. Chin J Traumatol 2001;4(4): Davis JC DJ, Heimbach RD. Hyperbaric Medicine: Patient selection, treatment procedures and side-effects.: Elsevier: New York, 1988: (Problem Wounds: The role of oxygen). The physiological role of adjuvant hyperbaric Edited by LIME Research Editor 10 P a g e