Design and Study Centre
Our study was a prospective non-randomized trial conducted in an 800 bedded tertiary care teaching center having super-specialty courses in neuroanesthesia and neurocritical care. The institute has a dedicated neuro ICU with 24-hour coverage by trained intensivists. At the time of this study the area had a combination of 8 ICU and high dependency beds (HDU), and henceforth we use the term ICU to refer to any of these bed types. The study was granted permission by the institute ethics committee (IEC) and was prospectively registered. Informed consent was obtained from all patients before participation in the study, and the trial was registered prospectively with the Indian clinical trials registry (CTRI/2017/07/015451). A change in the type of study design (as suggested by our institute ethics committee) lead to re-registration with the trial registry retrospectively and a new registration number was given (CTRI/2018/04/013247).
Patient recruitment
All adult patients of ASA physical status I and II over the age of 18 years (inclusive), with a single supratentorial space-occupying lesion posted for elective craniotomies were included. Moribund patients requiring emergency craniotomies, uncontrolled diabetics, severely cognitive impaired patients unable to follow simple instructions, and those who did not consent were excluded. After obtaining informed consent for participation, all patients and their family members were explained about the study. Those who understood and agreed to follow and adhere to the new ERAS protocol were included in the trial. The rest served as controls.
ERAS protocol Vs. Conventional Care An ERAS protocol bundle, based on the existing literature and that proposed by Hagen et al., was agreed upon by the Department of Anesthesiology and Critical care and the Department of Neurosurgery in conjunction with the Critical care nursing and dietetics divisions and approved by the institutional ethics committee ( vide approval No. IEC/AIIMS BBSR/PG THESIS/2017–18/18).The protocol consisted of primarily three segments – Pre-operative, intra-operative, and postoperative. (Fig. 1)
The pre-operative ERAS bundle began in Group ERAS (GrE) with a structured pre-operative counseling and education .The patientsand next of kin were informed about the elements of care of the multimodal ERAS protocol. An active patient and caregiver participation was encouraged to improve compliance. All patients in GrE received a pre-operative complex carbohydrate maltodextrin drink(Preload→) 100 grams in 200 mL of clear water the night before surgery, and repeated 50 grams in 100 mL water 2 hours preceding the surgery. (7)
All the patientsreceived pre-emptive analgesia (flupiritine maleate) 100 milligrams the night before surgery, repeated 2 hours before surgery. (8) The control group (GrC) did not receive the elements of care as mentioned above, and standard pre-operative fasting guidelines were followed.
Induction and maintenance of anesthesia were standard for both the groups with intravenous propofol (titrated toloss of verbal response), short-acting opioids (fentanyl – 2 mcg/kg bodyweight.), vecuronium (0.1 mg/kg body weight) and isoflurane titrated to minimum alveolar concentration (MAC) of 1-1.5. After induction, all GrE patients received scalp blocks with 20 mL 0.25% Bupivacaine. The Anaesthesia team performed the scalp block.Incision site infiltration with lignocaine 2% (10 mL), second hourly sugar monitoring, goal-directed fluid therapy, and intra-operative temperature monitoring weredone for both the groups. In addition to these measures, a nasogastric tube was placed in all Gr E patients.
Outcome Measures- Patients with a duration of ICU stay of < 48 hours, defined as the number of calendar days from ICU admission to the time of discharge from the ICU were recorded for each group as the primary outcome measure. The secondary measures were total episodes of visual analogue score (VAS) > 4,, insulin (Units) and fentanyl (micrograms) administered in the first 48 hours of ICU stay, and the total duration of hospital stay after surgery.
In the postoperative period, second hourly pain assessment (VAS) andeighth hourly glucose monitoring were done for the first 48 hours of ICU stay or till discharge from ICU whichever was earlier. In addition to intravenous paracetamol (1 gram) given three times daily to both the groups, all Gr E patients received 100 mg of Flupiritine Maleate three times a day through their nasogastric tubes. Early enteral feeding was started for all Gr E patients within the first 6 hours of ICU admission, provided there were no contraindications (such as an anticipated relook surgery) .The decision for enteral feeding was delayed until after the first successful extubation trial in the GrC as per unit protocol. Opioids were avoided in the postoperative period in both the groups, to be used as rescue analgesia if the VAS score was > 4.Foley’s catheter and surgical drains were removed on the first postoperative day for all Gr E patients as a part of the ERAS protocol. The decision for removal of indwelling catheters was left to the surgical team in Gr C. Patients in GrE who developed urine retention, or developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) could be recatheterized on a case to case basis.
Postoperative mechanical ventilation was a combined decision of the anesthesia and surgical teams, and the sedation protocol for these patients was similar for both groups of patients- involving an infusion of dexmedetomidine as the agent of first choice. Postoperative sugar control was strictly maintained through eighth hourly glucose monitoring for both the subset of patients. Patients whose blood glucose levels were above 180 mg %werestarted on an insulin infusion with second-hourly monitoring as per our institutional practice titrated to maintain between 120–180 mg%. Patients who were conscious and weaned off the ventilator and vasopressor support were ambulated or sat out of bed (for patients with hemiplegia/paresis) on the first postoperative day. This practice was standard of care and was followed for both sets of patients.
Discharge
The decision of discharge from the ICU was taken by the dedicated ICU team for both subsets of patients and decided after the combined neurosurgical and critical care team agreed. Discharge criteria were same for both groups, and included adequate pain control, afebrile state, cardiopulmonary stability, and being able to sit out of bed. Both subsets of patients werefollowed up till the day of discharge from the hospital.
Adherence;To maximize adherence, an ERAS checklist was attached to all eligible patients after obtaining consent. Before starting the study, a workshop was organized to train the nursing teams of both intensive care units and neurosurgery ward to familiarize the staff and resident doctors with the various elements of the ERAS protocol- this module was repeated twice during the study period to cater to changes in staff- mix .
Data Collected
Patient demographic data such as age, sex, body weight, ASA physical status, type and volume of the tumor, a pre-existing comorbid illness like hypertension, hypothyroidism, and diabetes mellitus were recorded in the patient data form. The total episodes of VAS scores above four, cumulative insulinadministered during 48 hours of ICU stay, and the total duration of hospital stay were recorded. Also, the dose of fentanyl used as rescue medication,and the incidence of any postoperative complications were recorded. The same experienced surgical team operated all the patients of both subsets.All patients received their allocated interventions.
Statistics
The sample size calculation was based on data obtainedfrom the medical records of the previous six months. Seventy percent of patients operated for supratentorial tumors by the same surgery and anesthesia team had apostoperative ICU stay of > 48 hours. It was hypothesized that the ERAS protocol could bring this down by 50%. For a 80% power, an alpha error of 5%,and10% attrition, a sample of 70 patients would be needed.
Descriptive statistics were used to compare the patient baseline characteristics. All continuous data which were normally distributed were analyzed using Student’st-test, whereas nonparametric data were analyzed using the Mann – Whitney U test. A chi-square test or Fisher’s exact test was used for qualitative variables. All the statistical tests were performed using the SPSS software, version 25.