This is a randomized controlled trial to compare the intravenous (IV) with the oral route for initial dose titration of morphine in 62 end-stage cancer
patients. All were strong opioid naïve and had severe opioid responsive pain, having scored 5 or more on a 0-10 Numerical Rating Scale (NRS).
The setting of care is the Pain and Palliative Care Clinic in the city of Calicut, state of Kerala (India) where 2000 new patients are seen every year and about 80%
of them present with severe pain. The routine clinical practice of the Authors of the paper is to administer bolus doses of IV morphine for immediate relief of severe pain followed by an appropriate
dose of immediate release oral morphine every 4 hours. The Authors had previously published their experience with IV morphine for fast titration in 1478 cancer patients (Palliative Medicine 2000;
Thirty-one patients were randomly allocated to the Intravenous Group (IV) and were administered:
a) metoclopramide 10 mg IV as an antiemetic; b) 1.5 mg of morphine administered slowly as an IV bolus every 10 minutes. Pain relief and adverse effects (in particular
drowsiness and respiratory depression) were assessed before each bolus. The end of the trial was considered when complete pain relief or drowsiness was achieved. The total dosage of IV morphine
required was converted to an oral morphine dose to be administered every four hours (example 9 mg of IV morphine to achieve pain relief = 10 mg of oral morphine every 4 hours) plus the same dosage
was used for rescue doses at a minimum interval of 1 hour.
Thirty-one opioid naïve patients were allocated to the Oral Group and titrated with 5 or 10 mg of oral morphine every 4 hours plus the same dosage for rescue doses
at a minimum interval of 1 hour.
In both groups, the patients were monitored every hour for 12 hours, then every day for two days and then every week with regard to: 1. pain relief after each dose,
2. Number of rescue medications, 3. adverse effects.
After 1 hour of morphine administration, the number of patients in IV group with total or satisfactory pain relief was 26 and only 8 in the oral group (p< 0.001).
However, after one day, the number of patients with satisfactory pain relief was similar in the two groups (p< 0.55).
Thirty, of the 31, patients in the IV group reached a satisfactory pain relief after 3 hours with dosages of morphine varying from 1.5 mg to 34.5 mg (median 4.5 mg)
whereas in the oral group only 76% of the patients had satisfactory pain relief after 12 hours (p<0.001) with a mean dose of 7.2 mg of oral morphine every 4 hours (range 2.5-15 mg).
After stabilization and satisfactory pain relief using IV morphine, the mean dose of oral morphine required was 8.3 mg (range 2.5-30 mg) every 4 hours. The ratio of
total IV requirement to control the pain to the stable oral morphine dose after 2-3 days varied between 1:0.5 and 1:3.3 (median 1:1).
Immediate side effects were drowsiness at the end of the IV trial in 11 patients and severe vomiting in 1 patient in the oral group. Delayed side effects were mainly
constipation, drowsiness and vomiting. Patients were treated with metoclopramide tablets 10 mg t.i.d and laxatives.
Why I chose this article
Even if the titration with strong opioids is commonly performed using immediate release oral morphine every four hours, there are some clinical situations such as severe
pain where pain relief has to be achieved as quickly as possible. This is the only prospective randomized study comparing titration with IV morphine compared to oral morphine. The results of fast
IV titration compared to oral titration with morphine are very encouraging in terms of efficacy and tolerability of the IV route.
Other studies that confirmed the fast pain relief with IV morphine titration:
1. Radbruch L et al. Intravenous titration with morphine for severe cancer pain: report of 28 cases. Clinical Journal of Pain 1999; 15/3 September : 173-8
2. Mercadante S. et al. Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion. Cancer 2002; 95: 203-8