Feasibility, safety, and outcomes of a stratified fast-track care trajectory in pituitary surgery

This prospective cohort study was performed among a consecutive group of pituitary tumor patients treated endoscopically between December 2016 and December 2018 in a tertiary reference center. There were two reference groups: the first consisted of all pituitary tumor patients operated in the same period but were not considered eligible for fast-track discharge; the second was a retrospective cohort consisting of patients treated endoscopically prior to the intervention between January 2010 and November 2016 (historic controls). The Ethical Committee of the Leiden University Medical Center approved the prospective part prior to the study (p16.091). Consent was obtained from each patient after full explanation of the purpose and nature of all procedures used. For the historic control group, the same ethical committee approved a waiver of medical ethical review (G19.011).

All patients were diagnosed with a pituitary tumor and underwent endoscopic transsphenoidal resection between January 2010 and December 2018 at our tertiary referral center, the Leiden University Medical Center in the Netherlands. From December 2016 onwards, patients were preoperatively assessed for eligibility for fast-track discharge. The systematic assessments were based according to a literature-based clinical protocol during a weekly pituitary multidisciplinary team meeting. Predefined reasons for ineligibility for the fast-track group were: need for emergency surgery (e.g. apoplexy), Cushing’s disease (CD), giant adenoma, craniopharyngioma, living far from the hospital, inadequate support network, and/or cognitive deficits. Directly after surgery, re-evaluation of the eligibility for fast-track discharge as well as an estimation of complication risks was performed by the treating neurosurgeon. Discharge was based on clinical grounds and only when deemed safe by the treating physician. This was re-assessed on a daily basis after surgery. Patients in the historic control group received care as usual.

Patients considered eligible for the fast-track care trajectory were instructed to actively participate in their own postoperative care by means of a standardized checklist which they had to report to the case manager on a daily basis after discharge. This checklist was composed to support patients to keep track of their fluid balance, weight, and relevant clinical signs and symptoms (Supplementary Table 1). Patients were instructed to report results digitally during the first 10–14 days after surgery. Those not capable of complying with our electronic surveillance were monitored through telephone consultation. The duration of the surveillance was dependent on the clinical judgment of the case manager and could be extended if deemed clinically necessary. Patients not eligible for fast-track discharge received care as usual up to December 2017, but along the way were also included in the outpatient monitoring after discharge. The surgical procedure has previously been published and was in line with existing guidelines [18‐20]. All patients received low-dose perioperative corticosteroids (hydrocortisone) until postoperative confirmation of adequate pituitary–adrenal axis function was performed through dynamic testing or a fasting cortisol. Postoperative sodium levels were determined on POD7 for all patients and/or in case of symptoms of hyponatremia.

All data, with the exception of the prediction of complications, were obtained in the context of routine care and gathered by means of review of the medical records and questionnaires. Questionnaires could be filled in either digitally or on paper, both shown to provide equivalent results [21]. The treating neurosurgeon was asked to report his assessment on a case report form, directly after surgery.

These included age, sex, comorbidities, tumor type, date of diagnosis, pituitary function, visual functioning, and cerebral nerve deficits. Comorbidities were categorized into diabetes mellitus, neurovascular, cardiovascular, pulmonary, ophthalmologic disease, or malignancies. Tumor types included: nonfunctioning pituitary adenoma, acromegaly (ACRO), CD, prolactinoma (PRL), TSH-producing adenoma, Rathke’s cleft cyst, or craniopharyngioma (Cranio). Pituitary function was defined as: (1) no deficits, (2) single hormone deficiency, (3) single hormone deficiency plus DI, (4) multiple hormone deficiencies, (5) multiple hormone deficiencies plus DI, and (6) DI alone. Visual functioning was defined as the presence of visual field deficits, or not. Prior treatments were described as: (1) no treatment, (2) prior medical (tumor) treatment, (3) prior surgery, and (4) prior radiotherapy.

Primary outcomes were feasibility, safety, ability to predict postoperative complications, patient-reported experience, and costs. Patient-reported outcomes were secondary outcomes.

Feasibility was defined as the proportion of patients allocated to the fast-track group, who were discharged 2–3 days after surgery and not readmitted within the fifth postoperative day (POD), which was often the date of discharge prior to the implementation of the protocol. Furthermore, adherence to the fast-track surveillance protocol was registered by means of the length of surveillance and the frequency and duration of fluid balance interventions.

Safety was defined as the occurrence of a severe complication after discharge (Clavien–Dindo grade III or higher) [22]. Complications of interest were readmission within 30 days (general), transient DI/permanent DI/delayed hyponatremia/new pituitary deficiencies (endocrine complications) and postoperative CSF leak/epistaxis/intracranial hemorrhage (neurosurgical complications). Transient DI was defined as necessity of treatment (desmopressin) up to 6 months after surgery. Permanent DI was defined as treatment for more than 6 months. CSF leaks during surgery with prompt closure were not considered a postoperative complication and were not a contraindication for early discharge. For readmissions, the primary reason of readmission, duration of readmission in days, and postoperative date of readmission were recorded.

The estimated risk of complications was evaluated immediately after surgery by the neurosurgeons to investigate whether this would help to differentiate between patients at risk of complications and those who were not. The likelihood of complications included transient DI, permanent DI, new onset of pituitary deficiencies, epistaxis, postoperative CSF leak, and intracranial hemorrhage. The likelihood of complications was dichotomized into not likely and possible, from which the sensitivity and specificity were calculated.

A comprehensive set of PROMs was administered at baseline (preoperatively) and 6 weeks after surgery. Changes in PROMs were calculated as between group differences corrected for baseline. Disease bother was measured through the Leiden Bother and Needs Questionnaire-pituitary (LBNQ-pituitary) [23], which was modified in order to make it suitable for perioperative repeated measurements. The total score ranges from 0 to 100, with higher scores indicating a greater disease bother or need for help. Health-related quality of life (HRQoL) was measured using the short form-36, from which physical and mental component scores can be calculated. These range from 0 to 100, with higher scores indicating better HRQoL [24]. Health status was assessed using the five-level EQ-5D index (Dutch tariff, anchored at 0 (as bad as death) and 1 (perfect health)), and the EQ-5D VAS (ranging from 0 to 100) [25, 26]. Higher scores indicate a better perceived health status. Visual functioning was assessed through the visual functioning questionnaire-25 (range 0 to 100), and higher scores indicate better visual functioning [27].

Patient-reported experiences were measured 4 weeks after surgery among patients in the fast-track group by means of a self-designed questionnaire and included experience of delivered care, sense of safety at home during the first 3 days at home, as well as the period after (day 4 through day 7). This questionnaire also assessed the self-perceived patient empowerment on a five-point Likert scale (range: “not at all” to “completely”) and the self-perceived optimal discharge date (range: −2 to +4 days).

Costs were estimated from a healthcare perspective, at price level 2019. Hospital care included the initial admission (regardless of duration) and all subsequent hospital care up to 30 days after surgery (including readmission, emergency room visits, outpatient clinic visits, e-mail, and telephone contacts). All healthcare use was assessed from patient records, except for outpatient clinic visits in the non-fast-track and historic cohort, which was set at two visits, unless hospitalization lasted for more than 30 days. Costs for surgery were derived from the Dutch Healthcare Authority [28, 29], and all other costs from Dutch reference prices designed to standardize economic evaluations (Supplementary Table 2) [30].

All statistical analyses were performed with SPSS 25.0 software (SPSS Inc., Armonk, NY, USA). Nominal variables are presented as frequencies with percentages, numerical variables as means and standard deviations (SD), or medians with interquartile ranges (IQR). Comparisons were made between the fast-track and non-fast-track groups, as well as between the historic group and the total group (fast-track and non-fast-track). Comparisons were performed through one-way ANOVA, Chi-square analyses, Fisher’s exact test, or general linear mixed models (GLM), where applicable. The sensitivity (Se) and specificity (Sp) were used to calculate the discriminative ability of the predictions, as approximated by ½(Se + Sp) [31]. Longitudinal analysis was performed via GLM analysis and results are presented as means with corresponding standard errors. For all analyses, the level of significance was set at p < 0.05 (two-sided). Missing data on the validated questionnaires were handled by parcel summary imputation [32].

The historic control group comprised of all patients surgically treated between January 2010 and December 2016, including those with diagnoses that were not considered eligible for fast-track surgery. In an attempt to compare the fast-track group with representative patients from our historical cohort, all comparisons were repeated after exclusion of patients with CD, Cranio, giant adenomas, and acute apoplexy (sensitivity analysis).