“Enhanced recovery after surgery – ERAS in elective craniotomies-a non-randomized controlled trial”

Our study was a prospective non-randomized assessor-blinded trial conducted in an 800 bedded tertiary center (training in neurosurgery, neuroanesthesia, and neurocritical care) as the doctoral thesis requirement of A.E. The institute has a dedicated neuro ICU with 24-h coverage by a dedicated team of doctors and nurses. 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 (CTRI/2017/07/015451). Informed written consent was obtained from all patients. A change in the study design (as suggested by the IEC) lead to retrospective re-registration (CTRI/2018/04/013247).

All adult patients of ASA physical status I and II over 18 years (inclusive), with a single supratentorial space-occupying lesion posted for elective craniotomies, were included. Moribund patients requiring emergency craniotomies, uncontrolled diabetics, severely cognitively impaired patients unable to follow simple instructions, and those who did not consent were excluded. Informed consents were obtained, and cohort assignments were based on the patients’ and family members’ agreement to be assigned to the ERAS protocol versus control.

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 – Preoperative, intra-operative, and postoperative. (Fig. 1).

This group was managed as per existing practices at our center- preoperative fasting, 2 h for clear liquids, and 6 h for solids, and no preemptive analgesics were prescribed. Induction and maintenance of anesthesia were with intravenous propofol (titrated to loss of verbal response), short-acting opioids (fentanyl – 2 mcg/kg body weight), vecuronium (0.1 mg/kg body weight), and isoflurane titrated to minimum alveolar concentration (MAC) of 1.0. Incision site infiltration with lignocaine 2% (10 mL), invasive arterial pressure monitoring with arterial blood gases on demand, point of care sugar monitoring, pulse pressure variation, and temperature management were available to all anesthetists at all times, but their use was not enforced.

Care in the ICU- Standard nurse-led analgesia and sedation management in the ICU followed second hourly documentation of Visual Analogue of pain (VAS) and Richmond Agitation Sedation Scales (RASS), aiming for a VAS < 4 and RASS between − 2 to + 1. Intravenous paracetamol (maximum dose of 1 g per day, unless contraindicated) followed by non-steroidal agents (NSAIDs) as required was administered. Fentanyl (1 mcg/kg body weight) was used only as rescue analgesia for VAS > 4. Dexmedetomidine (first choice) or propofol infusions were used for postoperative sedation of ventilated patients, midazolam being reserved for hemodynamically unstable ones. The unit has standard SOPs for insulin infusion to maintain blood sugars in the 110–180 mg% range. Patients whose blood glucose levels were above 180 mg %were started on an insulin infusion with second-hourly monitoring to reach the target range. Patients meeting pre-set criteria were extubated by the on-floor ICU team of doctors and nurses. However, starting enteral feeds, removing drains, urinary catheters, and ambulation awaited the ICU and neurosurgery consultant rounds the day after the surgery, as per unit protocol.

The preoperative ERAS bundle began in Group ERAS (GrE) with structured preoperative counseling and education. The patients and 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 received a preoperative complex carbohydrate maltodextrin drink (Preload®) 100 g in 200 mL of clear water the night before surgery and repeated 50 g in 100 mL water 2 h preceding the surgery [11]. Pre-emptive analgesia was administered- (flupiritine maleate) 100 mg the night before and repeated 2 h before surgery [12]. After induction, all patients received scalp blocks by the anesthetist with 20 mL 0.25% Bupivacaine. Fluid management was based on pulse pressure variation and normothermia ensured by warming blankets. A nasogastric tube was placed in all patients. In ICU, the patients received 100 mg flupiritine maleate eight hourly in addition to the routine protocol. Enteral feeding was started within 6 h of surgery, provided there were no contraindications (such as an anticipated relook surgery). Removal of catheters, drains, and ambulation was directed by a study team member without waiting for consultant rounds: patients who developed urine retention or developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) were re-catheterized on a case to case basis.

The discharge decision from the ICU was taken by the neurosurgical and critical care teams together. Discharge criteria were the 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 were followed up till the day of discharge from the hospital.

To maximize adherence, an ERAS checklist was attached to all GrE patient-files 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.

Duration of ICU stay defined as calendar days from ICU admission was the primary outcome. The secondary measures were total episodes of the visual analogue score (VAS) > 4, insulin (units) and fentanyl (micrograms) administered in the first 48 h of ICU stay, and the total duration of hospital stay after surgery.

All the interventions related to implementing the ERAS protocol were made by the research team belonging to anesthesia (A.E., S.J., S.N.), Critical Care (S.T.), and Neurosurgery (R.N.S). Members of the study team were not involved in the decision to discharge from the ICU or hospital.

All assessments and documentation (pain and sedation scores, analgesic and insulin doses, and stay in ICU and hospital) were made by ICU nurses not a part of the study team. After discharge from the ICU, the ERAS checklist was removed from the patient-files, and a blinded assessor collected the data for analysis. The data analyzer was unaware of the group allocation of the patients.

The sample size calculation was based on data obtained from the previous six months’ medical records. Seventy percent of patients operated for supratentorial tumors by the same surgery, and the anesthesia team had a postoperative ICU stay of > 48 h. It was hypothesized that the ERAS protocol could bring this down by 50%. For 80% power, an alpha error of 5, and 10% 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’s t-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.