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April 1998
Acute respiratory depression as a complication of nebulised morphine
Lang E, Jedeikin R. Can J Anaesth 1998; 45:60-62.
[ see abstract below ]
One way that we have been able to expand our pharmacologic armamentarium is by exploration of new routes of administration of old drugs. The last 10 years has seen an explosion of interest in techniques and technology for administering drugs across skin (creams, patches, electrotransport systems) and mucosa (nose, mouth, rectum). The lung provides an amazing surface area for drug absorption. However it is somewhat difficult to quantitate dosing of inhaled drugs in that characteristics of the delivery system can substantially affect the amount of drug absorbed.
Inhaled nebulized morphine has been reported anecdotally and in the medical literature to provide remarkable symptomatic relief of dyspnea particularly that experienced by patients with cancer. It has been much less effective for those whose dyspnea is due to COPD or interstitial lung disease. Irazuzuta et al. have reported preliminary pharmacokinetic data on intratracheal administration of fentanyl (Intens Care Med 1996; 22:129-133). Hydromorphone also has been used (Farncombe M, Supportive Care in Cancer 1994; 2:184-187)
The above-referenced report from Tel-Aviv University of severe respiratory depression after inhalation of 4 mg of nebulized MS to an elderly woman with metastatic lung disease provides an opportunity to consider the risks and benefits of this route for morphine
administration.
Neither the methods nor the discussion section of this paper mentions the delivery system used for this patient. Dershwitz and colleagues from the Harvard Medical School reported at the last ASA (Anesthesiology 87:A376, 1997) on the pharmacokinetics of morphine delivered by inhalation to normal volunteers using the AERx(tm) Pulmonary Drug Delivery System. These investigators compared 8 puffs of 2.2 mg/puff (17.6 mg over 7 min) with an 8.8 mg infusion delivered over 7 min. These doses were chosen on the basis of in vitro evidence that about � of the stated dose leaves the device as a "respirable aerosol". With this system, they found that peak blood levels were attained as rapidly
as those seen after the intravenous infusion described above. They calculated that approximately 2/3 of the medication actually was delivered to the lung.
Other, less sophisticated delivery devices, which lack laser-micromachined delivery holes, are likely to result in far less "respirable aerosol" than is delivered by the AERx(tm). When larger droplets are delivered, they often stick to the walls of the pharynx and larger airways with the result that far less medication is available for absorption in the small airways. However, the advantages of simplicity and cost savings may dictate the use of simpler devices. At least one hospice facility uses a simple flow-through nebulizer.
Dyspnea is a highly distressing symptom and is frequently a problem for patients with terminal cancer. Because patients with complex sources of suffering need multiple imaginative therapies to improve their comfort, I would strongly disagree with one of the conclusions of Dr. Lang's report: "Studies should be performed to determine if the administration of nebulised morphine is justified given the potential risks." The patient in this report had been receiving relatively small doses of morphine for a relatively short time. Clearly , relatively opiate naïve "patients receiving inhaled morphine [for the first time] should be closely monitored [with]...resuscitation equipment readily available." However, the tolerance to the respiratory depressant effects of opioids develops quickly and dyspneic patients should not be deprived of their many benefits.
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Purpose: To present a case of respiratory depression following the administration of nebulised morphine.
Clinical Features: A 74 yr-old. 51 kg woman with a history of hypertension controlled with 5 mg.day-1 enalapril and 50mg.day -1 atenol was admitted for evaluation of low back pain, loss of appetite, and weight loss. Investigation revealed advanced metastaic disease with a probable primary in the right lung. The patient�s pain was well controlled with 10 mg continuous release morphine po three times daily, and 10 mg immediate release morphine po for breakthrough pain as required. During the two weeks following the commencement of this treatment she occasionally complained of shortness of breath. Examination revealed a fully conscious patient with slight dyspnoea and mild wheezing which responded to oxygen 30% and nebulised bronchodilators.
An oncological consultation recommended 4 mg nebulised morphine and 4 mg dexamethasone in saline as treatment for the bouts of breathlessness. Approximately 15 min after the first administration of nebulised morphine the patient became markedly bradypneic (respiratory rate: 4-5 bpm), hypotensive (BP 70/40 mmHg), and responded only partially to command. The pupils were pinpoint. The trachea was immediately intubated and the lungs ventilated with oxygen 40% for four hours. Following this occurrence of respiratory depression, nebulised morphine was discontinued and no further events occurred.
Conclusion: Patients receiving inhaled morphine should be closely monitored and resuscitation equipment should be readily available.
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