Abstract

Introduction: During the course of healing and increasing the level of consciousness in traumatic brain injury (TBI) after reducing sedatives and dose of analgesics, TBI patients develop some complications, the most common of which are agitation and delirium. Agitation and delirium may deteriorate prognosis and prolong hospital stay. Considering the serious side effects caused by the conventional treatments for agitation and delirium, it is important to prioritize finding safer treatments with lower risks to manage delirium and agitation. Nowadays, melatonin therapy is considered to be effective.
Aim: Evaluation of the effect of melatonin on the incidence rate of agitation and delirium in TBI patients.
Materials and methods: In this double-blind clinical trial, 118 patients were studied. The participants were divided into two groups of A and B using blocked randomization. Then, group A was given 5mg/kg/h of oral melatonin at 9 p.m. every night, while group B only received synthetic oral placebo. In case of agitation, both groups were prescribed 0.02-0.04mg/kg/h of midazolam to reach Richmond score between -1 and 1. To control pain and reach visual analogue scale (VAS)<3, 0.02-0.04mg/kg/h of intravenous morphine was administered every hour. In case of delirium, based on the confusion assessment method for the intensive care unit (CAM-ICU) criteria, 0.02-0.04mg/kg/h of haloperidol was prescribed. Since the first day of ICU admission until the 10th day of admission, we evaluated and recorded the pain level based on VAS, the administered dose of morphine, the administered dose of midazolam, the incidence rate of delirium based on CAM-ICU and the administered dose of haloperidol every 12 hours. To analyze the data, the two groups were compared based on the frequency of requiring morphine, midazolam and haloperidol, as well as the incidence rates of agitation and delirium by performing Chi-square test in SPSS 11.
Results: In 118 cases, 97 (82.8%) were male and 21 (17.8%) were female, Mean age of 37.79 in melatonin and 36.54 years in placebo group (P=0.65). The incidence rate of agitation was significantly higher in the placebo group, compared to melatonin group (P=0.0001). The mean dose of midazolam administration was 7.86mg/kg/h in the melatonin group, while it was 12.79mg/kg/h in the placebo group (P=0.0001). No significant difference was observed in the mean dose of haloperidol between the melatonin and placebo groups. The mean administered doses melatonin of were 2.64 and 3.38mg/kg/h in the melatonin and placebo groups, respectively (P=0.313).
Conclusion: The incidence rate of agitation in patients taking placebo was significantly higher than in those receiving melatonin. In the early ICU admission hours, agitation could be managed and occurred less in patients administered melatonin (group A) rather than those in Group B, which in turn, diminished the administered dose of midazolam (mg/kg/h) to control agitation. In the early ICU admission hours, delirium was controlled more effectively in the melatonin group; however, there has been no significant difference between the two groups concerning the mean VAS scores.

Keywords

Traumatic brain injury, agitation, delirium, melatonin, hospitalization, pain, anxiety, hypotension, Poursina Hospital, midazolam, haloperidol, antioxidative effects, medication, irritability, sleep-wake cycle