This prospective randomized controlled clinical trial included 60 head-injured patients and was performed in the Trauma Intensive Care Units, Department of Anesthesia, and Intensive Care and Department of Neurosurgery, Assiut University Hospital (single Tertiary Hospital) between May 2013 and May 2017.
Inclusion criteria for the patients in this study were as follows: ASA I–III, patient between 18 and 80 years, Glasgow coma scale (GCS) ≥ 8, agitated and restless patients in need for sedation and close follow-up, diagnosis of TBI by CT or abnormal posturing, and placement of an intracranial pressure monitor at the discretion of the neurosurgical staff as a part of the standard of care. Exclusion criteria were as follows: patients who need mechanical ventilation on admission, AV block with HR < 45/min, and severe preadmission hemodynamic instability. For each patient, the following demographic data were collected from the trauma registry: sex, age, weight (kg), height (cm), BMI, Trauma Severity Score, and GCS on admission.
Allocated patients were randomized, using a program-generated random number table, into three groups; allocation concealment was done using opaque well-sealed envelopes which were opened sequentially for each allocated patient. Groups are based on the type of sedation used in the ICU; patients were randomized into three groups; dexmedetomidine group (n = 20): dexmedetomidine (Precedex® Dexmedetomidine HCl vial, HOSPIRA, INC) was infused in a loading dose of 1 μk/kg followed by I.V infusion of 0.4–1 μk/kg/h. The dexmedetomidine is supplied in a 2-ml vial of 100 μg/ml; each vial was diluted in 48 mL of normal saline in a syringe pump to yield a final concentration of 4 μg/ml and infused for 48 h.
Propofol group (n = 20): propofol 1% (Fresenius Kabi AB) in 20-ml ampoule was administrated as a loading dose of 1 mg/kg followed by maintenance dose of 1.5–4.5 mg/kg/h titrated to the desired effect. Propofol was infused in a 50-ml syringe pump for 48 h. Dexmedetomidine + propofol group (n = 20): dexmedetomidine were infused in a dose of 0.2 μg/kg/h and propofol were infused in a dose of 2 mg/kg/h for 48 h. Sedative agents were titrated to reach a goal of ICP< 20 mmHg and CPP> 60 mmHg with calm patients (controlling agitation, restlessness, and anxiety). After starting the infusion, strict and vigil monitoring of hemodynamic and respiratory parameters at regular intervals of 2 h for 48 h was done. Patients fulfilling the inclusion criteria were admitted to the Trauma Intensive Care Unit and were treated according to our standard protocol for treatment of TBI.
At ICU, to describe physiological changes, baseline parameters were observed and recorded, which included heart rate (HR), systolic, diastolic, and mean arterial blood pressures, respiratory rate, and pulse oximetry (SpO2). Intracranial pressure (ICP) was monitored by an intraparenchymal catheter placed by author neurosurgeon using CODMAN® MICROSENSOR® ICP Transducer. The abovementioned parameters were measured at 2, 4, 8, 12, 24, 36, and 48 h from admission to the ICU. Neurological assessment was done for all patients by GCS and agitation scale by modified Richmond Agitation-Sedation Score (RASS) [3].
The length of ICU and hospital stay and adverse events were recorded daily for each studied patient and defined as hypotension (systolic blood pressure [SBP] < 90 mmHg or MAP < 65 mmHg), hypertension (SBP > 160 mmHg), bradycardia (heart rate [HR] < 40 bpm), and tachycardia (HR > 120 bpm). Assessment of delirium was performed every 12 h after cessation of sedation or as needed according to the patient’s condition using the confusion assessment method (CAM) for ICU.
Informed consent according to the criteria set by the local research ethics committee in our center had to be obtained in writing before surgery. If consent could not be obtained because the patient was in a coma or dysphasic, consent was obtained from relatives. Through explanation, the purpose of the study and how data will be treated with respect and confidentiality were provided to the participants.
Statistical plan
Data were statistically described in terms of range, mean ± standard deviation (± SD), median, frequencies (number of cases), and percentages when appropriate. Comparison of quantitative variables between studied groups was done using the one-way ANOVA test. As for the samples for comparing categorical data, chi-square (χ2) test was performed. A probability value of less than 0.05 was considered relative frequencies statistically significant. All statistical calculations were done using computer programs Microsoft Excel version 7 (Microsoft Corporation, NY, USA) and SPSS 20 (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows (Fig. 1).