Postoperative Delirium In The NICU: Hormonal Risk Factors
In neurosurgery, pituitary adenoma ranks as the second most common brain tumor. Recent advances in endoscope-assisted transsphenoidal surgery have revolutionized tumor resection, reducing complications. However, postoperative complications, particularly endocrine-related issues, remain critical in neurosurgical intensive care units (NICUs). Notably, postoperative delirium, intricately linked to hormonal changes, presents significant challenges. This cohort study explores the connection between hormone level shifts after pituitary tumor resection and postoperative delirium in the NICU.
THE BACKGROUND OF THE STUDY
The prevalence of pituitary adenoma as the second most common primary brain tumor has underscored the significance of advancing neurosurgical techniques. The evolution of endoscope-assisted transsphenoidal surgery has enabled more thorough tumor excisions and minimized complications [1]. However, despite these strides, the realm of postoperative complications, particularly those related to endocrine function, holds clinical importance. Such complications pose intricate challenges for patients in neurosurgical intensive care units (NICUs) during the critical early postoperative period [2].
The emergence of postoperative delirium (a complex neurological disturbance characterized by acute and fluctuating changes in cognition and consciousness) is particularly concerning [3]. This phenomenon has been linked to hormonal fluctuations, potentially impacting patients’ recovery and outcomes [4]. Extensive stays in the NICU due to delirium have been associated with increased healthcare costs and heightened mortality rates [5]. Thus, understanding the risk factors associated with postoperative delirium becomes pivotal.
While limited attention has been directed toward pituitary tumor-associated delirium, a handful of case reports have hinted at its significance [6]. Even cases of idiopathic pituitary insufficiency have shown prolonged delirium experiences [1]. Based on these cues, it is hypothesized that fluctuations in hormone levels following pituitary tumor resection may play a crucial role in the onset of postoperative delirium.
This cohort study was carried out to address this knowledge gap involving patients who underwent endoscope-assisted transsphenoidal pituitary adenoma resection. The study aims to shed light on the potential perioperative risk factors contributing to postoperative delirium within the NICU setting.
THE STUDY METHOD
The study employed a retrospective design to investigate the potential perioperative risk factors for postoperative delirium in patients who underwent endoscope-assisted transsphenoidal pituitary tumor resection. The patient selection spanned from January 2018 to May 2022, including those admitted to the Department of Neurosurgery at Southwest Hospital.
The research encompassed 360 patients diagnosed with pituitary tumors who underwent endoscope-assisted transsphenoidal resection. Exclusions were made based on factors like pre-existing dementia or cognitive impairment, communication difficulties, and certain medical conditions. Propensity scores matched patients with or without delirium, controlling for age, sex, and tumor size. Ultimately, 348 eligible patients were included in the study.
Delirium diagnosis followed the Diagnostic and Statistical Manual of Mental Disorders criteria, including altered mental status, inattention, altered consciousness, and disorganized thinking. Delirium assessments were performed using CAM-ICU (Confusion Assessment Method of the Intensive Care Unit).
The data collection process involved extracting various characteristics and clinical data, such as patient demographics, adenoma classification, endocrine levels, and biochemical indicators. Statistical analysis was conducted using propensity score matching, t-tests, and regression analysis.
In essence, the study retrospectively enrolled patients who underwent pituitary tumor resection, utilized propensity score matching for analysis, and adhered to established diagnostic criteria for delirium assessment.
ANALYSIS
The study employed statistical analysis to investigate its research objectives. A 1:3 propensity-score matching was conducted using R version R4.2.1 from the R Foundation for Statistical Computing, employing the nearest-neighbor method without replacement. A caliper value of 0.2 was utilized for this matching process. Subsequently, data was analyzed using IBM SPSS Statistics version 24.0 and graphed using GraphPad Prism 7.04 software. Categorical variables were juxtaposed using chi-squared tests or Fisher’s exact tests, while continuous data were reported as mean ± standard deviation and discrete data as median ± interquartile range. The study employed statistical tests such as Student’s t-test and Mann–Whitney U test to compare independent variables. Regression analysis focused on variables with significant differences in two-group comparisons. A significance level of p < 0.05 was taken as statistically substantial, and a standard mean difference (SMD) less than 0.1 indicated negligible differences between groups.
RESULTS
The research yielded significant findings regarding patient characteristics and the impact of delirium on prognosis and hormonal factors in postoperative pituitary adenoma patients.
Patient Characteristics
Before propensity score matching (PSM), there was a difference in tumor size between the delirium and non-delirium groups, with a standard mean difference (SMD) of 0.249. However, after PSM, no significant differences were observed in age, female sex, or tumor size between the matched groups (SMD=0.076, 0.019, 0.063). Baseline data comparisons showed no significant differences, including adenoma classification, hospital days, and operation times.
Prognosis and Characteristics of Patients with Delirium
The modified Rankin scale score at discharge indicated that patients with postoperative delirium had a more significant percentage of poor prognosis (mRS=1) than those without delirium (48.22% vs. 0.93%). Additionally, assessments of delirium occurrence (CAM-ICU) and severity (ICDSC and RASS) over specific time intervals after surgery revealed noteworthy trends. Delirium occurrence rapidly increased 24 hours after surgery, and high RASS scores were significantly associated with delirium.
Univariate and Multivariate Analysis
Univariate and multivariate analyses confirmed that delirium was an independent risk factor for poor neural prognosis in postoperative pituitary adenoma patients at discharge. The odds ratio (OR) was 88.471, with a 95% confidence interval (CI) of 10.994–711.908.
Hormonal and Blood Risk Factors for Delirium
Comparisons of routine blood and hormonal variables between delirium and non-delirium groups unveiled notable differences. Patients without delirium showed higher secretion of insulin-like growth factor 1 (IGF-1) within 72 hours of surgery and corticotropin-releasing hormone (CRH) after 72 hours of surgery. Conversely, blood glucose (GLU) levels were higher in the delirium group 72 hours after surgery. Univariate analysis suggested associations between serum potassium ions at admission, serum sodium ions within 72 hours of surgery, GLU after 72 hours of surgery, and CRH after 72 hours of surgery, with the occurrence of delirium. Multivariate analysis further confirmed that the elevation of GLU 72 hours after surgery independently increased the risk of delirium.
These results provide new insight into the intricate relationship between postoperative pituitary adenoma patients, delirium, patient characteristics, and hormones.
DISCUSSION
This research aimed to identify perioperative risk factors for postoperative delirium in patients who underwent endoscope-assisted transsphenoidal surgery for pituitary adenomas. Notably, the study found significant associations between hormone levels and delirium. Lower insulin-like growth factor-1 (IGF-1) levels and corticotropin-releasing hormone (CRH) were tightly linked to postoperative delirium. Additionally, high blood glucose (GLU) levels after surgery were shown to be a contributing factor to delirium development. At the same time, serum potassium and sodium levels also emerged as independent risk factors for delirium [1].
The clinical importance of postoperative delirium was emphasized, as it represents a severe complication marked by cognitive dysfunction and confusion. Furthermore, delirium was identified as an independent risk factor for the subsequent development of dementia, suggesting that strategies to prevent delirium could potentially mitigate long-term cognitive impairment [1].
Hormone associations in delirium were explored, revealing a complex relationship. Lower IGF-1 and higher growth hormone (GH) levels were associated with delirium [1]. However, research literature has presented divergent findings in this area. While some studies support hormone-dementia connections, others suggest variations due to factors like timing of blood collection and underlying medical conditions [1].
Propensity score matching (PSM) was employed to reduce bias related to age, gender, and tumor size, enhancing the robustness of the analysis [1]. The debate surrounding the necessity of routine glucocorticoid supplementation for pituitary adenoma patients was discussed, particularly in postoperative delirium. Although recent trials question the conventional approach, they did not consider postoperative delirium in their assessments [1].
The study highlighted the significance of maintaining internal homeostasis in preventing postoperative delirium. Notably, higher serum potassium and sodium levels and raised blood sugar levels were associated with an increased risk of delirium after surgery [1]. Nonpharmacological multicomponent interventions were suggested to prevent and reduce delirium duration in intensive care unit (ICU) patients [1].
Lastly, the impact of the surgical approach was considered. Endoscope-assisted transsphenoidal surgery, a standard method for treating pituitary adenomas, was examined concerning postoperative delirium. While some studies reported no significant effects on cognitive changes, others speculated that physical discomfort, such as headaches and nasal pain, could influence the occurrence of delirium [1].
This research underscores the intricate connections between hormone levels, blood glucose, and developing postoperative delirium in patients with pituitary adenomas. Effective intervention strategies targeting these factors could improve patient outcomes. However, additional research is needed to comprehensively understand the complexities of postoperative delirium and establish practical preventive and management approaches [1].
LIMITATIONS OF THE STUDY
- Surgical Approach Bias: The study mainly focused on endoscope-assisted transsphenoidal surgery, potentially introducing a selection bias by excluding patients who underwent other surgical approaches. This limitation might restrict the generalizability of the findings to a broader population of pituitary adenoma patients.
- Complex Hormone Relationships: The associations between hormone levels and delirium revealed in the study are complex and multifaceted. The intricate nature of hormone interactions makes it challenging to establish definitive causal relationships, and other factors might influence the observed associations.
- Hormone Timing and Variability: Hormone levels can vary over time and can be influenced by various factors, including medical conditions and time of blood collection. These temporal fluctuations and variations may introduce confounding variables that diminish the results’ reliability.
- Limited Intervention Evidence: While nonpharmacological multicomponent interventions were suggested for preventing and reducing delirium in ICU patients, there needs to be a standardized practice. Also, the study does not provide concrete interventions for mitigating the risk of postoperative delirium, leaving a gap in actionable recommendations.
- Exclusion of Psychological Factors: The study primarily focuses on medical and physiological factors, neglecting potential psychological or psychosocial factors that could contribute to developing delirium. Such factors might interact with the physiological aspects of delirium and warrant consideration.
- Sample Size and Diversity: The study’s sample size and demographic homogeneity (e.g., age, gender, and surgical approach) might limit the external validity of the findings. A more diverse and more extensive sample could provide a better representation of the population under study.
- Lack of Long-Term Follow-up: The study’s scope is limited to the immediate postoperative period, needing long-term follow-up to investigate potential cognitive outcomes or delayed effects of delirium on patients’ health.
- Single-Center Design: The study was likely conducted at a single center, which might limit the generalizability of the results to a broader healthcare context with varying practices and patient populations.
- Confounding Variables: Despite the use of propensity score matching (PSM), unobserved or unmeasured confounding variables might still affect the results, influencing the associations between the examined factors and postoperative delirium.
- Lack of Delirium Prevention Strategies: While the study identifies risk factors, it does not delve into specific interventions to prevent or manage postoperative delirium. Further research is needed to translate these findings into actionable strategies for clinicians.
It’s important to note that while these limitations provide critical insights, they do not invalidate the study’s findings. Instead, they emphasize areas for improvement and further investigation in future research endeavors.
CONCLUSION
In conclusion, this research sheds light on the intricate interplay between hormonal factors and postoperative delirium in endoscope-assisted transsphenoidal surgery for pituitary adenomas. The study’s identification of lower IGF-1 and CRH levels and elevated post-surgery blood glucose associated with delirium offers valuable insights. However, the study’s exclusive focus on a specific surgical approach and limited sample diversity limits generalizability. The multifaceted nature of delirium and the absence of concrete interventions underscore the need for further research and interdisciplinary collaboration to improve prevention and management strategies.
References
- Liu, J., Qian, J., Wang, X., Lin, J., Yang, S., Hu, R., Xian, J., Feng, H., Chen, Y., & Tan, B. (2023). Identifying hormones and other perioperative risk factors for postoperative delirium after endoscope-assisted transsphenoidal pituitary adenoma resection: A retrospective, matched cohort study. Brain and behavior, 13(7), e3041. https://doi.org/10.1002/brb3.3041.
- Goudakos, J. K., Markou, K. D., & Georgalas, C. (2011). Endoscopic versus microscopic trans-sphenoidal pituitary surgery: a systematic review and meta-analysis. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery, 36(3), 212–220. https://doi.org/10.1111/j.1749-4486.2011.02331.x.
- Witlox, J., Eurelings, L. S., de Jonghe, J. F., Kalisvaart, K. J., Eikelenboom, P., & van Gool, W. A. (2010). Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA, 304(4), 443–451. https://doi.org/10.1001/jama.2010.1013.
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Publishing. https://psycnet.apa.org/record/2013-14907-000
- Davis, D. H., Muniz Terrera, G., Keage, H., Rahkonen, T., Oinas, M., Matthews, F. E., Cunningham, C., Polvikoski, T., Sulkava, R., MacLullich, A. M., & Brayne, C. (2012). Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain : a journal of neurology, 135(Pt 9), 2809–2816. https://doi.org/10.1093/brain/aws190.
- Marcantonio, E. R., Simon, S. E., Bergmann, M. A., Jones, R. N., Murphy, K. M., & Morris, J. N. (2003). Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery. Journal of the American Geriatrics Society, 51(1), 4–9. https://doi.org/10.1034/j.1601-5215.2002.51002.x.
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