• Gabriela R Lauretti, Marcelo V Perez, Marlene P Reis, and Newton L Pereira.
• Hospital das Clínicas, Department of Biomechanical and Medical Rehabilitation of the Locomotor Members, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. grlauret@fmrp.usp.br
• J Clin Anesth. 2002 Mar 1;14(2):83-6.

Study ObjectivesTo examine analgesia and adverse effects following transdermal application of nitroglycerine (a nitric oxide generator) combined with oral morphine, in cancer pain patients.DesignRandomized, double-blind study.SettingTeaching hospital.Patients36 patients suffering from cancer pain.InterventionsPatients were divided into two groups (n = 18). All patients were regularly taking oral amitriptyline 50 mg at bedtime. Pain was evaluated using a 10-cm visual analog scale (VAS). The morphine regimen was individually adjusted to a maximal oral dose of 80 to 90 mg/day, to maintain the VAS score less than 4/10 cm. When patients complained of pain (VAS equal or greater than 4/10), despite taking 80 to 90 mg of oral morphine daily, the transdermal test drug was supplemented as follows: the control group received a placebo patch daily, and the nitroglycerine group received a 5-mg/24-hour nitroglycerine patch daily. Patients were free to manipulate their daily morphine consumption at the time the test drug was administered, to keep VAS less than 4/10 cm. After the introduction of the transdermal test drug, patients were evaluated by the staff on a weekly basis as outpatients, over four consecutive weeks.Measurements And Main ResultsThe groups were similar in respect to demographic data and VAS pain scores before the treatment. The daily consumption of oral morphine was smaller in the nitroglycerine group compared with the control group after the 14th day of evaluation (p < 0.002). Patients from the control group in general complained of somnolence, compared with the nitroglycerine group.ConclusionTransdermal nitroglycerine was an effective coadjuvant analgesic. In conjunction with its opioid tolerance sparing function, delivery of nitric oxide donors together with opioids may be of significant benefit in cancer pain management in delaying morphine tolerance and decreasing the incidence of adverse effects related to high doses of opioids.

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