Background
Morphine is the main stay of analgesic management in cancer patients experiencing severe pain (Numerical Rating Scale {NRS} score >7 on a scale of 0-10). Analgesic titration can be done either by intravenous (IV) morphine by slow infusion technique or by rapid IV bolus technique. Our study compares the analgesic efficacy of two technique of morphine titration (bolus vs. infusion) by calculating total rescue dosage in one week after analgesic titration.

Methods
After institutional Ethical committee approval, patients were randomized in two groups of 70 each by computer generated random numbers. In morphine bolus group, IV morphine 1.5 mg bolus given every 10 minutes till NRS<4 is achieved. Total IV dose converted to oral dose (1:1) and was administered every 4 hourly. In morphine infusion group, IV bolus Morphine 0.05mg/kg body weight administered followed by 0.025mg/kg/hour IV infusion. Pain was reassessed every 30 minutes using numerical rating scale (NRS). Infusion rate of morphine was doubled if NRS unchanged. Infusion was increased to 50% when NRS was between 4 and baseline. If NRS<4, same infusion was continued. Once the NRS<4 for two consecutive hours, total IV dose for 24 hours was calculated and converted to oral morphine (1:3) in 6 divided doses in 24 hours. Serum morphine level was calculated in both groups. Total rescue dosages in one week were calculated. Primary Outcome of this study was to note number of rescue (NRS>=4) doses of oral morphine in a day at one week.  For rescue (NRS>=4) analgesia, 4th hourly dose was prescribed. Secondary outcomes recorded was Ramsay sedation scores (RSS), respiratory rate (RR), oxygen saturation (SpO2), serum morphine levels (SML), nausea and vomiting in both groups.
Results
Demographics were comparable in both groups.  The incidences of nausea, vomiting, oxygen saturation, respiratory rate were comparable in both groups. NRS significantly lower in Group I compared to Group II at 10 min (6.43±1.80 vs 7.12±1.79; P=0.01) and at 20 min (4.86±2.24 vs 6.10±2.10; P=0.01) but comparable at rest intervals in both groups. Ramsay sedation scores was significantly lower in Group I compared to Group II at 20 min (1.88±0.694 vs 1.58±0.60; P=0.01) and 30 min (2.02±0.75 vs 1.68±0.58; P=0.01) but comparable at rest intervals in both groups. Duration of adequate analgesia achieved was significantly lower in group I compared to group II (43.24 ± 32.25 min vs 93.73± 80.05 min; P<0.001). The total rescue dosage in one week after discharge from palliative care unit was significantly higher in group I as compared to group II (1.46 ±2.58 vs 0.72 ±1.47; P=0.03).Serum morphine levels were significantly lower in group I than group II (15.50 ± 14.03 ng vs 58.53 ± 154.22 ng; P<0.01). 
Conclusion
Infusion and Bolus morphine provides effective analgesia in palliative cancer patient. Sedation scores were higher in bolus morphine group and rescue dosages required were also higher in bolus morphine group. Serum morphine levels also higher in infusion group. On the basis of above findings, we suggest that infusion morphine is a better option for morphine titration.

COMPARISON OF TWO TECHNIQUES (BOLUS MORPHINE VS. MORPHINE INFUSION) OF ANALGESIC TITRATION WITH INTRAVENOUS MORPHINE IN PALLIATIVE CANCER PATIENT - A PROSPECTIVE RANDOMIZED STUDY