Influence of perioperative blood pressure regulation on postoperative delirium in patients undergoing head and neck free flap reconstruction

This study was approved by the local ethics committee of the Medical Faculty of RWTH Aachen University (EK 144-18) and all methods were in accordance with the relevant guidelines and regulations.

Data from 433 patients who underwent reconstruction in the head and neck region with microvascular free flaps in our department of oral and maxillofacial surgery between 2011 and 2019 were retrospectively analyzed. The patients were surgically treated for malignant or non-malignant diseases. The data were obtained from clinical notes and operation reports. Patients with neurologic diseases, psychiatric diseases, or substance use disorders (except for excessive alcohol consumption and smoking) were excluded from the study. Patients with incomplete or missing data were also excluded.

Further analysis was performed for all 55 patients with POD and 55 matched patients without POD with respect to surgical procedure parameters (i.e., transplant type, transplant location, and tracheotomy). The diagnoses for patients without POD and patients with POD, respectively, were adenocarcinoma (n = 2 and n = 0), ameloblastoma (n = 2 and n = 1), atrophies (n = 0 and n = 1), basal cell carcinoma (n = 0 and n = 2), medication-related osteonecrosis of the jaw (n = 0 and n = 1), melanoma (n = 0 and n = 1), Merkel cell carcinoma (n = 2 and n = 0), myxoma (n = 1 and n = 0), nerve sheath tumor (n = 0 and n = 1), osteomyelitis (n = 2 and n = 1), squamous cell carcinoma (n = 40 and n = 43), squamous cell carcinoma metastasis (n = 1 and n = 0), osteoradionecrosis of the jaw (n = 1 and n = 2), sarcoma (n = 2 and n = 2), salivary gland carcinoma (n = 1 and n = 0), and trauma (n = 1 and n = 0).

All surgical procedures were performed under general anesthesia with intravenous or volatile narcotics, muscle relaxants, and opioids. Each patient’s MAP and SBP were monitored via an intraarterial catheter. Blood pressure was adjusted as needed using intravenous norepinephrine. The patients were intubated via tracheotomy tubes or oral tubes and had a central intravenous catheter. After surgery, the patients were admitted to the intensive care unit (ICU). Postoperative intensive care management included sedation and mechanical ventilation until at least the first postoperative morning. In addition, blood pressure was adapted to a target SBP of > 125 mmHg until the first postoperative morning. 5000 IU of heparin was administered subcutaneously three times daily for seven days. Enteral nutrition was administered via nasogastric tube until the patient was able to swallow. If POD occurred, the patients received psychoactive medications (clonidine, haloperidol, quetiapine, risperidone, pipamperone), and a psychiatrist was consulted if needed.

Variables included demographic data (such as sex and age) and clinical data (such as body mass index (BMI), American Society of Anesthesiologists score (ASA), excessive alcohol consumption, smoking, diagnosis of preoperative arterial hypertension, preoperative antihypertensive medication, transplant type, transplant location, tracheotomy, operation time, blood transfusion, intraoperative SBP, intraoperative MAP, postoperative SBP, postoperative MAP, transplant revision, transplant success, length of hospital stay, length of ICU stay, and postoperative complications). In line with commonly used definitions, smoking was defined as a condition if the patients had smoked daily for a period of more than 6 months at the time of the preoperative anesthesia preparation interview, and excessive alcohol consumption was defined as a condition if the patients consumed more than 40 g of pure alcohol per day (for men) or more than 20 g of pure alcohol per day (for women) at the time of the preoperative anesthesia preparation interview [25, 26]. A diagnosis of preoperative arterial hypertension was recorded if the diagnosis was confirmed according to the discipline-specific guidelines. Only prescribed medications were defined as permanent medications. Transplant revision was defined as a surgical revision of the anastomosis with return to the operating room, and transplant success was defined as transplant survival until discharge from the hospital. Sepsis, systemic inflammatory response syndrome, acute renal failure, and patient death were defined as postoperative complications.

Intraoperative blood pressure values were obtained from the graphical representations of blood pressure values in the clinical records (measured with the IntelliVue X2 M3002A device [Philips Medizin Systeme Boeblingen GmbH, Boeblingen, Germany] by two investigators [mean value was used in case of discrepancy between investigators]), and postoperative blood pressure values were obtained from an electronic recording system (measured with the IntelliVue X2 M3002A device [Philips Medizin Systeme Boeblingen GmbH, Boeblingen, Germany] and recorded with the IntelliSpace Critical Care and Anesthesia ICCA data management system [Philips Medizin Systeme Boeblingen GmbH, Boeblingen, Germany]). Intraoperative blood pressure was measured invasively via an arterial catheter; postoperative blood pressure was measured invasively via an arterial catheter or non-invasively via a blood pressure cuff. Non-invasive blood pressure measurement data were used only when invasive blood pressure measurement data were not available. The patient’s SBPs and MAPs were recorded intraoperatively at 15-min intervals and postoperatively at 5-min intervals. The reference values for SBP and MAP were obtained from the routinely performed blood pressure measurement on the day before surgery or, if not available, calculated as the mean of all preoperative blood pressure measurements in the operation room before the induction of anesthesia. The time of anesthesia induction was defined as the time of administration of the induction medication. Intraoperative and postoperative SBP and MAP were determined as absolute minimum and maximum values. The deviations in SBP and MAP were calculated as the absolute difference between the maximum value and the reference value for upward deviation and as the absolute difference between the reference value and the minimum value for downward deviation. If the maximum value was lower than the reference value or the minimum value was higher than the reference value, the deviation was set to zero. All blood pressure values were analyzed for patients without POD until discharge from the ICU; all blood pressure values were analyzed for patients with POD until the occurrence of POD.

The diagnosis of POD was based on the Confusion Assessment Method (CAM) for ICU or by a validated chart review method, considering the words “delirium” and “delirious”, in line with the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) [1, 27‐29]. All cases of delirium identified through chart review were validated by a second investigator. With regard to CAM, a diagnosis of POD was established when an acute onset and fluctuating course, inattention, and disorganized thinking or an altered level of consciousness were detected [21, 27]. This study did not distinguish between hyperactive, hypoactive, and mixed subtypes of POD.

The patients were divided into those with POD and those without POD. The patients were also divided into two classes according to ASA (> 2 and ≤ 2). Descriptive analyses were performed separately for patients without POD and patients with POD, with continuous variables expressed as medians with interquartile ranges (IQRs) and categorical variables expressed as numbers with percentages (%). Testing for differences between patients with POD and patients without POD was performed using McNemartest for categorical data or Wilcoxon signed rank test for metric data. Multivariable conditional logistic regression analysis was performed for variables that showed significant differences between patients with and without POD. Receiver operator characteristics analyses were performed for intraoperative MAPs, and the theoretical optimal cut-off MAP values for the prediction of POD were determined by the calculation of the Youden index [30]. The diagnostic accuracy was analyzed by calculating the area under the curve [31]. P < 0.05 were considered statistically significant. No correction for multiple testing was performed. The statistical analysis was performed using SPSS version 26 (SPSS, IBM, New York, USA).

The analyzed study population included 110 patients out of a total of 433 patients, 55 of whom had POD. All 55 patients with POD were matched with patients without POD in terms of transplant type, transplant location, and tracheotomy (Table 1). The groups differed in terms of age (p = 0.011). The groups did not differ in terms of sex (p = 0.486), ASA (p = 0.063), BMI (p = 0.206), excessive alcohol consumption (p = 0.307), smoking (p = 0.307), preoperative arterial hypertension (p = 1.000), preoperative antihypertensive medication (all p > 0.05), operation time (p = 0.580), or blood transfusion (p = 0.327). No difference was observed between the groups for transplant success (p = 1.000), with 1 (1.8%) transplant loss (1 anterolateral thigh flap) in the group of patients without POD and 2 (3.6%) transplant losses (1 radial forearm flap, 1 anterolateral thigh flap) in the group of patients with POD.

Compared to patients without POD, patients with POD underwent more transplant revisions (p < 0.001), with 17 (30.9%) transplant revisions compared to 3 (5.5%) transplant revisions. Patients with POD also had a higher rate of complications (p < 0.001), with 19 (34.5%) patients with POD having complications compared to 1 (1.8%) patient without POD having complications, and longer hospital stays (p < 0.001), with a median of 23 (IQR 22) days compared to a median of 17 (IQR 10) days for those without POD. Furthermore, patients with POD had longer ICU stays (p < 0.001), with a median of 7 (IQR 11) days compared to a median of 2 (IQR 1) days for those without POD.

In the 55 patients with POD, the median time of POD onset was on the second postoperative day (IQR 3 days).

The intraoperative and postoperative blood pressure values for SBP and MAP differed between patients with POD and patients without POD (Table 2).

Patients with POD had a lower intraoperative minimum MAP than patients without POD (p < 0.001), with a median of 60.0 (IQR 10.0) mmHg compared to a median of 65.0 (IQR 5.0) mmHg (Fig. 1).

Patients with POD had a higher postoperative maximum SBP than patients without POD (p = 0.005), with a median of 184.0 (IQR 33.0) mmHg compared to a median of 171.0 (IQR 29.0) mmHg (Fig. 2). Patients with POD had a lower postoperative minimum SBP than patients without POD (p = 0.003), with a median of 78.0 (IQR 30.0) mmHg compared to a median of 92.0 (IQR 17.0) mmHg (Fig. 2). Patients with POD had a lower postoperative minimum MAP than patients without POD (p < 0.001), with a median of 56.0 (IQR 11.0) mmHg compared to a median of 62.0 (IQR 10.0) mmHg (Fig. 2). In addition, patients with POD had a higher upward postoperative SBP deviation than patients without POD (p = 0.010), with a median of 51.0 (IQR 46.0) mmHg compared to a median of 29.0 (IQR 40.0) mmHg (Fig. 3).

The multivariable regression analysis identified intraoperative minimum MAP (odds ratio [OR] 1.246, 95% confidence interval [CI] 1.057–1.472), p < 0.001) as a predictor for POD (Table 3). Patients with lower intraoperative minimum MAPs were more likely to develop POD. Receiver operating characteristics analysis for intraoperative MAP (area under the curve [AUC] 0.822, 95% CI 0.744–0.900, p < 0.001) determined that the theoretical optimal cut-off value for predicting POD was ≤ 62.5 mmHg (sensitivity 0.727; specificity 0.800).