UHM 2016, Vol. 43, No. 1 – SEIZURES DURING HBO2 THERAPY: Retrospective analysis
Seizures during hyperbaric oxygen therapy: retrospective analysis of 62,614 treatment sessions A. Hadanny, M.D. 1,2,3, O. Meir, B.A. 1, Y. Bechor, B.A. 1, G. Fishlev, M.D. 1 , J. Bergan, S. Efrati, M.D. 1,2,3,4 1 2 3 4
The Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
CORRESPONDING AUTHORS: Amir Hadanny –
[email protected] and Shai Efrati –
[email protected] ______________________________________________________________________________________________________________________________________________________
ABSTRACT
Introduction: Hyperbaric oxygen (HBO2) therapy is considered to be a generally safe therapy. However, data regarding seizure incidence during HBO2 therapy as a clinical presentation of central nervous system(CNS) related oxygen toxicity are conflicting (ranging from 1:10,000 to 1:600 seizures:hyperbaric sessions). The risk for seizures is of significant importance for the growing population of patients suffering from chronic neurological disorders such as traumatic brain injury and stroke who are treated with HBO2. The aim of this study was to evaluate the incidence of seizures during HBO2 therapy in a large cohort of patients and determine whether patients with known chronic neurological disorders are at increased risk. Methods: Retrospective analysis of 2,334 patients treated at the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Israel,
between June 2010 and December 2014. Patients were grouped into one of three categories according to indication for HBO2 therapy: Category A– nonneurological indications; Category B – neurological indications; and Category C – acute indications. Results: A total of 62,614 hyperbaric sessions, administered to 2,334 patients, were included in the analysis. The overall incidence of seizures during hyperbaric sessions was 0.011% (1:8,945), occurring in seven (0.3%) patients. Only one patient had a clear oxygen toxicity-induced seizure, with an overall incidence of 1:62,614. Conclusions: Seizures induced by oxygen toxicity during HBO2 therapy are extremely rare. Moreover, in relation to oxygen-induced seizures, HBO2 therapy can be considered safe for patients suffering with chronic neurological disorders except for uncontrolled epilepsy.
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Introduction Hyperbaric oxygen (HBO2) therapy is being utilized for a growing number of patients with a wide diversity of comorbid illnesses. In particular, the number of patients with chronic neurological disorders such as traumatic brain injury and stroke has grown significantly. Patients with chronic neurological disorders are being referred for HBO2 therapy for non-healing wound indications (such as diabetic ulcers and crush injuries) and for the neurotherapeutic effects of HBO2 therapy [1-3].
The possibility that oxygen can induce hyperactivation of the central nervous system (CNS) was first suggested in 1878 [4]. Breathing hyperbaric oxygen can culminate in grand mal seizures, secondary to so-called oxygen toxicity, with or without preceding symptoms and signs. CNS hyperactivation and the development of seizures depend upon the partial pressure of oxygen and the duration of exposure [5]. The exact mechanism underlying CNS-related oxygen toxicity is not fully understood. One suggested mechanism involves reactive
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KEYWORDS: hyperbaric oxygenation, hyperbaric oxygen therapy, central nervous system oxygen toxicity, complications, adverse effects, side effects Copyright © 2016 Undersea & Hyperbaric Medical Society, Inc.
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UHM 2016, Vol. 43, No. 1 – SEIZURES DURING HBO2 THERAPY: Retrospective analysis oxygen species during HBO2 therapy that cause membrane lipid peroxidation and enzyme inhibition and/or modulations that lead to alterations in brain metabolism and its related electrical activity [6]. There is no clear evidence that seizures are related to oxygen induced metabolic changes, however, an increase of glucose utilization precedes the onset of electrophysiological manifestations of CNS oxygen-toxicity [5]. Another suggested mechanism relates to increased nitric oxide (NO) levels in the brain, which may cause vasodilation in cerebral vessels and further increase oxygen delivery to the brain [7]. HBO2 therapy is considered to be a generally safe therapy. However, as clinical presentations of CNSrelated oxygen toxicity, seizures are reported with conflicting incidence range, from 1:10,000 and up to 1:600 seizures:hyperbaric sessions [8]. HBO2-induced seizures are defined as brief, oxygen-related, generalized tonic-clonic convulsions usually occurring toward the end of the treatment [5]. Non-oxygen-related seizures in epileptic patients treated with HBO2 therapy, even though rare, should be differentiated from oxygen toxicity-related seizures [5]. Interestingly, in some cases where there is an epileptic focus secondary to circulatory and metabolic disturbances, HBO2 may even abort seizures by correcting these abnormalities [9]. CNS-related oxygen toxicity risk factors include fever, hypoglycemia, carbon monoxide poisoning, hypercapnia, alcohol dependence and several medications (such as antidepressants, disulfiram, tramadol and cephalosporins) [5,10]. In addition, neurological disorders such as cerebral palsy, head trauma, stroke, autism and others are thought to lower seizure threshold [5,11]. The aim of this study was to evaluate the incidence of seizures during HBO2 therapy in a large cohort of patients and determine whether patients with known neurological disorders are at increased risk. Methods The study included all patients treated in the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Israel, between June 2010 and December 2014 (since June 2010, adverse effects were strictly recorded in the medical records). Data collected
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retrospectively from patients’ medical files included age, sex, chronic diseases, medications, indication for HBO2, HBO2 protocol (pressure and duration), number of sessions, side effects and reason for stopping treatment. The study was approved by the Helsinki Ethics Committee of Assaf Harofeh Medical Center. Patient categorization Patients were categorized into one of the following three groups: Category A – Patients with non-neurological indications including non-healing wounds, nonneurological radiation injury, osteomyelitis, avascular necrosis (AVN), complex fractures, Crohn’s disease and idiopathic hearing loss. Category B – Patients with neurological disorders due to stroke (both ischemic and hemorrhagic), traumatic brain injury, cerebral palsy, pervasive developmental disorder and radiation injury to the brain. Category C – Patients with acute indications for HBO2 including decompression sickness, carbon monoxide (CO) poisoning, acute limb ischemia or central retinal artery occlusion. Pre-HBO2 therapy evaluation Prior to the first session all patients were evaluated by a hyperbaric physician. Chest X-ray was obtained for each patient. Electrocardiogram (ECG) was performed in patients with a history of cardiovascular disease. History of epilepsy or seizures mandated a seizure-free interval of at least six months and a normalized electroencephalogram (EEG). Before each session, heart rate, blood pressure and temperature were obtained in all patients. Blood glucose was measured before each session in diabetic patients. Contraindication for HBO2 therapy Closed pneumothorax was a contraindication for HBO2 therapy. Relative contraindications included active uncontrolled bronchial asthma, severe obstructive pulmonary disease and pregnancy (depending on the urgency of the indication for HBO2 therapy). Patients with fever did not receive HBO2 therapy until the fever was under control with antipyretic medications or resolved.
Hadanny A, Meir O, Bechor Y, et al.
UHM 2016, Vol. 43, No. 1 – SEIZURES DURING HBO2 THERAPY: Retrospective analysis HBO2 therapy protocols HBO2 therapy was performed in a multiplace chamber equipped with video cameras and an intercom for patient observation. In addition, a registered nurse certified as a hyperbaric attendant was present inside the chamber during each session for patients’ care. Patients were treated five times per week with different protocols depending on the indication: 100% oxygen at 1.5 atmospheres absolute (atm abs) for 60 minutes with no air breaks and 0.8-meter-per-minute compression and decompression; 100% oxygen at 2 atm abs for 90 minutes with five-minute air breaks every 30 minutes and 1-meter-per-minute compression and decompression; and 100% oxygen at 2.4 atm abs for 90 minutes with five-minute air breaks every 30 minutes and 1-meter-per-minute compression and decompression. In addition, decompression sickness HBO2 treatments were performed according to U.S. Navy Treatment Tables: USN 5, USN 6, USN 6A [12]. Oxygen was supplied via masks or hoods. In-chamber seizure protocol In cases of suspected seizures during the treatment, the nurse attendant removed the patient’s mask or hood, examined the patient by advanced cardiac life support (ACLS) protocols and checked the patient’s blood glucose. The on-site physician then decided whether anti-convulsions drugs such as benzodiazepines should be given. Whether these medications were given or they were not, the patient was immediately decompressed and removed from the chamber for further evaluation. Statistical analysis Data are expressed as frequencies and percentages for non-parametric variables. Univariate analysis was performed using chi-square/Fisher’s exact test to identify significant variables (p
