Authors

1. Klugar, Miloslav PhD
2. Nytra, Ivana MS
3. Bockova, Sona MS
4. Klugarova, Jitka PhD
5. Kelnarova, Zuzana PhDr
6. Mareckova, Jana PhD

Abstract

Review question/objective: What is the effectiveness of hyperbaric oxygen therapy (HBOT) on the mortality of patients with craniotrauma?

Background: Craniotrauma and traumatic brain injury (TBI) is a major health problem worldwide and across all ages. It is a major cause of death and disability.1,2 Disability, as a result of TBI, has significant functional, social and economic consequences.2,3 According to the Institute of Health Information and Statistics in the Czech republic, TBI occurs at a frequency of 150 cases per 100,000 inhabitants which is about 36 000 per year; in 2009, 32,589 cases was hospitalized.4 Traumatic brain injury in the age group of 45 years was the leading cause of death in 2003;1 however, more recent studies showed a variation in age groups and a shift towards older adults, especially in high income countries.5 A TBI incidence of 150 to 300 cases per 100,000 people per year has been reported in North America and Europe. Over 200 cases per 100,000 are admitted to hospital in Europe. The incidence is even worse in low-income and middle-income countries.6 The World Health Organization estimates that TBI will be the third highest cause of global mortality and disability by 2020.7

Mass et al.,8 reported that TBI is classified by clinical severity, as determined by Glasgow Coma Scale (GCS); structural damage, as determined by computer tomography scans (CT) or magnetic resonance (MR); and the mechanism of TBI, whether closed or penetrating. There are three recognized degrees of TBI: mild; moderate; and severe.8,9,10 Traumatic brain injury could appear as a monotrauma, which means that only the brain is affected by injury. Traumatic brain injury could also manifest as part of a polytrauma, in which injury of two or more physical regions or organ systems are present, with at least one of the injuries being life-threatening.11 According to clinical and experimental results reported by Adamidese et al.,3 brain damage may not solely be caused by primary injury alone, but may progress during the following hours and days as secondary damage.3,12 Menon13 analogously stated that the basic principle for neuro-intensive care is that ischemia due to injury leads to further damage of brain tissues. The causes of secondary damage can be intracranial (brain lesions, edema, increased intracranial pressure, seizures, vasospasm, and infection) or general (hypotension, hypoxia, hyper/hypocapnia, hyper/hypoglycemia, anemia, coagulopathy, pyrexia, electrolyte imbalance, and infection).3 According to Gopinath et al.14 and Bouma et al.,15 the reduction of the brain blood flow and brain supply occurs within the first 24 hours. A lack of oxygen leads to a reduction of oxidative phosphorylation. The resources of glucose obtained from anaerobic glycolysis are used for output of energy.This process causes an excessive accumulation of lactate and deprives the energy for protein synthesis. Bergsneider et al.,16 Lifshitz et al.,17 Verweij et al.18 and Sahni et al.19 reported that this inefficient anaerobic metabolism leads to a reduction of energy in cells and initiates a cascade of biochemical processes that causes mitochondrial dysfunction, prolonged metabolism and death of cells. Ng et al. reported that cell death, such as necrosis and apoptosis, does not appear only in the areas immediately surrounding the site of injury, but also in further areas.20 Van der Brink et al. also presented results that showed the significant correlation of the partial pressure of oxygen in brain tissue ischemia and the end outcome.21

Many standard therapeutical approaches can be used for the care of traumatic brain injury patients, with the exception of standard intensive care monitoring. the specific values that should be measured and calculated include intracranial pressure, cerebral blood flow, cerebral perfusion pressure, jugular blood oxygen and lactate. The general aim for the care of traumatic brain injury patients is to optimize cerebrovascular haemodynamics including head elevation to 30[degrees], sedation, paralysis, barbiturate-induced coma, cerebrospinal fluid drainage, artificial ventilation-appropriate oxygenation, osmotherapy, therapeutic hypothermia, hyperventilation, decompressive craniotomy.3,8 Hyperbaric oxygen therapy (HBOT) is not used as standard therapy.3,25

Hyperbaric oxygen therapy as a potential treatment has been discussed since the beginning of hyperbaric medicine.12 Hyperbaric oxygen therapy is characterized by inhalation of pure oxygen (FiO₂ = 100%) in a hyperbaric chamber under pressure that is higher than atmospheric pressure, which is 1 ATA (atmosphere absolute).22,23 The range of pressure used for HBOT is between 1.5 ATA and 3 ATA for 30 to 120 minutes.3,12,19,22,24-29 An inhalation of oxygen at a pressure of 3 ATA increases partial pressure of arterial oxygen to 200 kPa and more,which leads to the dissolution of O₂/100ml blood in plasma from 6.6 to 6.8 ml. This quantity of oxygen is sufficient for the metabolic needs of basic vital organs and tissues.30 According to Huang and Obenhaus,22 HBOT was shown to be neuro-protective in many neurological diseases. Theoretically, the usage of HBOT should lead to a decrease in brain cell damage as well as mortality. Pressure that is above atmospheric increases oxygen delivery to brain cells and enhances aerobic metabolism, which leads to the restoration of mitochondrial functions.25 The clinical studies of varied design, including randomized controlled trials (RCTs), quasi-experimental, and case studies, were focused on substantiating the effect of HBOT on the damaged brain as a result of TBI. Patients included into these studies had suffered from acute or chronic TBI of mild to severe degree, both in civilian and military environment. Adults with TBI of varied causes were also included. The size of patient groups was below 170 patients. The examined HBOT was set from 1.5 ATA for 60 minutes to 2.4 ATA for 90 minutes. The number of HBOT sessions received by patients was between30 to 40.19,23-29,31 Most of the studies investigated the effect of HBOT alone or as an additional therapy to standard regimen.19,26,27,29,31 Other studies compared outcomes in patients who had underwent HBOT against those who were treated by standard regimen or NHO.24,28 Rockswold et al.25 compared HBOT combined with NBH against standard regimen. Investigators were focused on examining heterogeneous outcomes using various scales, including Glasgow Outcome Scale (GOS),25 Disability Rating Scale (DRS), Rancho Los Amigos Scale (RLAS),19 and Glasgow Coma Scale (GCS).19,23-29,31 A range of monitored variables were also examined, including intracranial pressure (ICP), continuous metabolic monitoring (microdialysis of lactate, glucosis, pyruvate), critical level of brain tissue PO₂, cerebral blood flow (CBF), oxygen toxicity markers (IL-6, IL-8), and mortality.24,25,27

The Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Cochrane Library and PROSPERO register were searched for systematic reviews conducted on the same topic. A systematic review focused on HBOT in the context of TBI was previously conducted in 2004 by Bennett et al.32 and published in 2012 by the same authors.33 The title of the systematic review from 2012 was "Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury".33 This systematic review was conducted according to Cochrane methodology. Authors included solely RCTs that compared the effects of treatments with HBOT against those without HBOT. Participants were patients suffering from acute TBI as a result of blunt injury and had been admitted to intensive care unit or intensive neurosurgical units. Authors divided outcomes in two groups: primary (functional outcomes and mortality) and secondary (activities of daily living, ICP, magnetic resonance imaging, progress in GCS, adverse effects of HBOT, and cost-effectiveness). Compared to the systematic reviewss conducted by Bennett et al.,33 we will follow Joanna Briggs Institute methodology and we will not focus only on RCTs but also on other types of study designs as well. For many reasons, including financial, technical, capacity etc., it is particularly difficult to conduct RCTs of high quality in the field of hyperbaric medicine. On the other hand, there are a lot of studies of high quality with designs other than RCTs. As specified in our inclusion criteria, we do not solely include acute TBI but will also include chronic TBI. Bennett et al.33 included studies with patients below the age of 18. We will therefore exclude any studies that involved children. Moreover, it is particularly important to look at the critical status of patients with acute craniotrauma and the initiation of HBOT, as some authors have recommended postponing HBOT until the patient is stabilized.34 Collectively, we will consider the initiation of HBOT in acute craniotrauma patients as part of the intervention for the systematic review.

1. Within the first 24 hours

2. After 24 hours

3. After 48 hours

4. After "stabilization" of patients (one week).

Our systematic review will be conducted at the end of 2014, more than two years since the systematic review by Bennett et al.33 was written, thus more recent studies could be found.

This review will undertake rigorous, systematic, consecutive and logical steps, which are aimed to critically appraise, summarize, analyze, and interpret collected data to present existing knowledge about the effects of HBOT on mortality of adults with cranial trauma.