HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Selecting neuromuscular-blocking drugs for elderly patients.

The physiological changes that occur with increasing age can have significant effects on the pharmacokinetics of neuromuscular-blocking drugs. Changes in cardiac output can affect drug distribution and therefore the speed of onset of neuromuscular block. A decrease in muscle mass and increase in body fat with age can also affect their distribution. The deterioration in renal and hepatic function associated with aging affects the clearance and elimination of many neuromuscular-blocking drugs. The effects of these physiological changes on the pharmacokinetics of neuromuscular-blocking agents may not become apparent clinically in healthy individuals until the age of at least 75 years. There is very little evidence to suggest any alteration in the sensitivity of the neuromuscular junction to neuromuscular-blocking drugs with increasing age. Neuromuscular-blocking drugs that undergo a significant degree of organ-dependent elimination, such as pancuronium bromide, vecuronium bromide, rocuronium bromide and doxacurium chloride, may have a significantly prolonged duration of action in elderly patients. These drugs can be used safely in elderly patients if the anaesthetist is aware of their altered pharmacokinetics in this patient group. Appropriate changes must be made to drug dosage and dose intervals. As the pharmacokinetic changes can be unpredictable, monitoring of neuromuscular block is strongly advised when using these drugs in such patients. The risk of residual block occurring postoperatively after the use of pancuronium bromide increases with age. The duration of action of mivacurium chloride may also be prolonged in the elderly; this change has not been demonstrated to be a result of an alteration in plasma cholinesterase activity. In contrast, there is no evidence of an alteration in the action of suxamethonium chloride (succinylcholine chloride) with increasing age. Atracurium besilate and cisatracurium besilate undergo predominantly organ-independent elimination. Onset of block with these two drugs may be prolonged in the elderly, but their clinical duration of action does not alter significantly with age, making them particularly suitable for use in this patient group. Although atracurium besilate may cause histamine release, there is little evidence of it producing haemodynamic changes in the elderly. Its (1R,1R')-isomer, cisatracurium besilate, has very little direct or indirect cardiovascular effect and is, therefore, the most suitable nondepolarising agent to use in elderly patients.