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Intensive Care Unit, Kanazawa University Hospital, Kanazawa, JapanDepartment of Anesthesiology and Intensive Care Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
Thirst is a prevalent distressing symptom often reported by patients in the intensive care unit (ICU). Little is known about the association of thirst with delirium.
Objective
We aimed to investigate the relationship between thirst and delirium.
Methods
This retrospective cross-sectional study enrolled 401 patients who were evaluated for thirst intensity in the ICU between March 2017 and October 2017. We assessed thirst intensity on a scale of 0–10 (with 10 being the worst) and defined intense thirst as a score ≥8. If intense thirst persisted for more than 24 hours, we defined it as persistent intense thirst. Delirium was screened using the Intensive Care Delirium Screening Checklist. Propensity score matching and inverse probability of treatment weighting analyses were performed.
Results
Of 401 patients, 66 (16.5%) had intense thirst sensation for more than 24 hours. After matching, patients with persistent intense thirst showed an increased risk for delirium compared with those without persistent intense thirst (odds ratio, 4.95; 95% confidence interval, 2.58–9.48; P < 0.001). Propensity score weighted logistic regression analysis also indicated that persistent intense thirst was significantly associated with delirium (odds ratio, 5.74; 95% confidence interval, 2.53–12.99; P < 0.001).
Conclusion
Intense thirst persisting for more than 24 hours was associated with increased risk for delirium.
The sensation of thirst results in a complex physiological drive to drink. Critically ill patients often experience distressful episodes of intense thirst during their stay in the intensive care unit (ICU). In an assessment of 10 symptoms, thirst was regarded as having the greatest intensity according to 70.8% of 171 patients in the ICU, and it was the second most prevalent symptom.
Thirst can be stimulated by either increased plasma osmolarity (osmotic thirst) or marked decreases in plasma volume (hypovolemic thirst). Central osmoreceptor neurons stimulate the release of arginine vasopressin peptide, and the low volume and pressure sensors in the kidneys increase circulating renin-angiotensin levels. The released angiotensin II promotes aldosterone secretion to retain sodium and water. Acting in harmony, these central and peripheral signals activate specific sites in the brain to stimulate the conscious perception of thirst.
Neuroimaging studies have shown that the anatomic origin of thirst is in the anterior wall of the third ventricle, anterior cingulate, parahippocampal gyrus, insula, and cerebellum. These brain regions are also associated with complex functions, including emotional behavior and thought.
Delirium is defined as the acute onset of cerebral dysfunction with a change or fluctuation in baseline mental status, inattention, and either disorganized thinking or an altered consciousness level.
Preventing, detecting, and treating delirium have become one of the most important challenges for critical care providers. Adequate pain management and promoting sleep-wake cycles are key to effectively treating patients at high risk for delirium in the ICU setting.
It is also important that any other sources of stress experienced by patients should be assessed and managed appropriately.
Over the past decade, there have been several studies regarding risk factors for delirium as well as pharmacological and nonpharmacological interventions to prevent delirium. However, little is known about the association between thirst and delirium. We hypothesized that patients experiencing intense thirst have a significant risk for delirium. In this study, we aimed to determine whether persistent intense thirst is strongly associated with delirium development.
Methods
Study Design and Participants
This study was approved by the ethics committee of our institution (approval number 2018–70). This single-center retrospective cross-sectional study reviewed data obtained from our institutional database from March 2017 to October 2017. The participating institution had 22 mixed medical-surgical ICU beds and a closed ICU system. We retrospectively identified adult patients (aged ≥18 years) who were examined for thirst intensity during their ICU stay. In our institution, patients were routinely asked to report about their thirst at least twice a day. We began to assess thirst intensity from their first ICU day. Thirst intensity was assessed using the numeric rating scale (NRS) of 0–10.
Anchor words for thirst intensity were “no thirst” = 0 and “worst possible thirst” = 10. Self-report with NRS was used because it is the gold standard for symptom assessment. Validity of the NRS has been established.
Orientation was confirmed if it was between −1 and +1 on the Richmond Agitation-Sedation Scale before thirst evaluation. When patients were deeply sedated or could not express their sensation, we scored it as “unmeasurable.” We reassessed thirst intensity on the next day in such cases and continued this process until the time of ICU discharge. We excluded patients whose thirst intensity score was incomplete or remained unmeasurable until ICU discharge. We also excluded patients who underwent surgery of the oral cavity because it could affect the thirst sensation.
Definition of Persistent Intense Thirst
We defined intense thirst as a score ≥8, based on a previous study.
If intense thirst persisted for more than 24 hours, we defined it as persistent intense thirst.
Thirst was managed by primary nurses, and the management comprised providing ice and ice-cold water sprays, application of lip and oral moisturizers, and maintaining appropriate fluid volume.
Data Collection
Demographic and clinical characteristics of patients, including age, sex, body mass index, history of dementia, laboratory values, medications (opioids and dexmedetomidine), first 24-hour Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation, continuous renal replacement therapy (CRRT), and presence of delirium, were extracted. Data on laboratory values were also extracted when the patient's thirst intensity was at the maximal value.
Outcomes
The primary clinical outcome was delirium during ICU stay, which was assessed using the Intensive Care Delirium Screening Checklist. The Intensive Care Delirium Screening Checklist, including the Japanese version, is a valid, reliable, and feasible tool for detecting delirium in ICU patients; a score ≥4 was defined as clinical delirium.
Sensitivity and specificity of the Confusion assessment method for the intensive care Unit (CAM-ICU) and the intensive care delirium screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: a single-center study in Japan.
We divided the patients into two groups based on their thirst intensity score: persistent intense thirst group and without persistent intense thirst group. The two-sample t-test or Wilcoxon rank-sum test was used, as appropriate, to compare continuous variables. For categorical variables, the chi-square test or Fisher's exact test was used. A propensity score (PS) matching analysis was performed to reduce the effects of selection bias and potential confounders between each group. PS was calculated based on a logistic regression model with potential confounding variables (age, sex, body mass index, APACHE II score, SOFA score, type of admission [surgical or medical], neurological disease, blood urea nitrogen, sodium, plasma osmolarity, dementia, diabetes mellitus, dexmedetomidine use, benzodiazepine use, calcium antagonist use, opioid use, mechanical ventilation, and CRRT) using clinical knowledge. Two groups were matched based on 1:4 nearest neighbors matching method. A PS difference of 0.15 was adopted as the maximum caliper width for matching. The standardized difference test was used to measure covariate balance. Logistic regression was used to evaluate the association between persistent intense thirst and delirium in matched groups. In addition, the inverse probability of treatment weighting (IPTW) analysis was performed to evaluate the sensitivity of the results by estimating propensity scores used to weigh individual observations. The IPTW analysis adjusts the confounding factor and has the advantage of evaluating causal effects without reducing sample size. All P-values were two-tailed, and P < 0.05 was considered statistically significant. We used STATA 14.2 (StataCorp, College Station, TX) and R statistical software (version 3.5.0; R Foundation for Statistical Computing, Vienna, Austria) for the analysis. Our missing values were handled using complete-case analysis.
Results
This study enrolled 401 patients. Figure 1 shows the patient flow diagram. A total of 163 patients (40.6%) experienced intense thirst during their ICU stay, and 66 (16.5%) had sensation of intense thirst for more than 24 hours (persistent intense thirst). An episode of delirium occurred in 47 (11.7%) of the 401 patients. The baseline characteristics of patients are presented in Table 1. Before the matching, APACHE II and SOFA scores, blood urea nitrogen, sodium, and plasma osmolarity were significantly higher in the persistent intense thirst group than in the without persistent intense thirst group. Dexmedetomidine, opioid, and calcium antagonists were the drugs more frequently used by patients with persistent intense thirst than by those without persistent intense thirst. Moreover, a greater proportion of patients with mechanical ventilation and CRRT were observed in the persistent intense thirst group than in the without persistent intense thirst group.
PS was estimated using logistic regression models with potential confounders, which had c-statistics of 0.80. According to PS, 65 patients with persistent intense thirst were matched with 261 patients without persistent intense thirst. The absolute standardized differences in the covariates between groups were improved after matching (Table 1). In the logistic regression model, patients with persistent intense thirst showed an increased risk for delirium than did patients without persistent intense thirst (odds ratio, 4.95; 95% confidence interval, 2.58–9.48; P < 0.001) (Table 2). In the IPTW analysis, the absolute standardized differences in the covariates were controlled well (Fig. 2). Persistent intense thirst was also significantly associated with delirium (odds ratio, 5.74; 95% confidence interval, 2.53–12.99; P < 0.001) (Table 2).
Table 2Odds Ratios of Persistent Intense Thirst for Delirium in Propensity Matching and IPTW Analyses
Model
Odds Ratio (95% CI)
P-value
Unadjusted
7.75 (4.02–14.94)
<0.001
Propensity matching
4.95 (2.58–9.48)
<0.001
IPTW
5.74 (2.53–12.99)
<0.001
CI = confidence interval; IPTW = inverse probability of treatment weighting.
Fig. 2Standardized differences of general characteristics before and after adjustment in the IPTW analysis. IPTW = inverse probability of treatment weighting; SOFA = Sequential Organ Failure Assessment; APACHE = Acute Physiology and Chronic Health Evaluation; CRRT = continuous renal replacement therapy; BMI = body mass index.
In this study, we demonstrated that among patients who could report their sensation of thirst, approximately 40% of patients complained of a strong sensation of thirst during their ICU stay. If intense thirst did not resolve and persisted for more than 24 hours, it was significantly related to delirium. To our knowledge, this is the first study to reveal the association between thirst sensation and delirium among ICU patients.
The interaction of pain and delirium is well known.
Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development.
Clinical practice guidelines for the prevention and management of pain, agitation/Sedation, delirium, Immobility, and sleep disruption in adult patients in the ICU.
Thirst is a common complaint and a source of distress for many critically ill patients. Like pain, this unpleasant symptom may cause frustration, anger, anxiety, and agitation, which are associated with delirium onset. In addition, intense thirst, which possibly persists overnight, may interfere with sleep quality. Delirium prevention and treatment is essential to improve sleep quality,
Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development.
Clinical practice guidelines for the prevention and management of pain, agitation/Sedation, delirium, Immobility, and sleep disruption in adult patients in the ICU.
Clinical practice guidelines for the prevention and management of pain, agitation/Sedation, delirium, Immobility, and sleep disruption in adult patients in the ICU.
Moreover, thirst is induced by decreased plasma volume (hypovolemic thirst). Studies on elderly medical patients have consistently reported that dehydration is a risk factor for delirium.
The role of fluid deficit in the pathogenesis of delirium remains unclear; the possible explanations for this include tissue hypoperfusion (especially cerebral and renal), increased concentration of drugs (e.g., opioids) and/or their metabolites in a depleted intravascular volume, and decreased renal elimination of drugs (e.g., opioids) and/or metabolites.
Available evidence suggests that assisted fluid administration may help prevent and reduce delirium, although such evidence is based on studies in patients with cancer.
Changing pattern of agitated impaired mental status in patients with advanced cancer: association with cognitive monitoring, hydration, and opioid rotation.
Strong thirst sensation urges people to drink water, which can be an absolute solution. However, critical illness prevents patients from drinking as much water as they want. A nil per os status or fluid restriction is prevalent in the ICU. Optimal fluid management is one of the methods for alleviating thirst when oral intake is insufficient. Intensive care providers usually monitor cardiac output, filling pressure as well as urine output, and fluid balance to achieve goals of fluid therapy. However, integrating the entirety of information for optimal fluid management is complex in critically ill patients.
In addition, fluid-restrictive strategies are often used as a standard practice for special types of surgery or for patients with acute respiratory distress syndrome based on several studies that show an association between fluid overload and worse outcome.
Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study.
National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N Comparison of two fluid-management strategies in acute lung injury.
Moreover, aggressive and active fluid removal through diuretics and renal replacement therapy is necessary in some cases to obtain consecutive negative fluid balance, which is also related to patient outcomes.
reported that a high dose of furosemide is an important predictor of thirst. These types of fluid management may put the patients at risk for relative volume losses.
Although dehydration (broadly defined as inadequate fluid intake) and hyperosmolar state have often been recognized as major stimuli of thirst, they have not been consistently correlated with patients' thirst reports. Several studies have failed to show an association between thirst and biochemical markers of fluid deficit or dehydration.
identified specific conditions such as mouth breathing due to hypoxia and stomatitis as possible etiologies of thirst. Furthermore, common dipsogenic medications, such as opioids, serotonin reuptake inhibitors, antihypertensive drugs and proton pump inhibitors,
are frequently used in the ICU. Besides the optimal fluid therapy, switching opioids to nonopioids could be one of the options to palliate intense thirst sensation.
However, further research is needed to confirm whether these aggressive thirst treatments have some beneficial effects on delirium prevention.
Our study has several potential limitations. First, our data showed associations rather than cause and effect because of the study's cross-sectional design. Further well-designed study is needed to clarify the association. Second, the sample size was relatively small because this study was conducted in a single center. Third, we did not assess patients' sleep quality, which is proposed to be strongly associated with delirium. Finally, the occurrence of delirium in this study was less frequent than that in other studies. To evaluate thirst intensity, patients needed to be able to communicate well because thirst intensity was based on self-report. Thirst intensity of patients with impaired communication, including those with advanced dementia or severe neurological disorders, which are possible risks of delirium, could not be assessed by self-report. Therefore, we could not include such patients in this study. Although our findings require further investigation, they contribute to existing knowledge on thirst sensation, which is one of the most common distressing symptoms in the ICU.
Conclusions
Our study found that intense thirst sensation was prevalent in the ICU and that thirst persisting for more than 24 hours was significantly associated with increased risk for delirium. Therefore, critical care providers should assess and monitor patients' thirst intensity. Further study is required to examine whether alleviating the burden of thirst has an impact on patients at high risk for delirium.
Disclosures and Acknowledgments
The authors thank the physicians, nursing staff, and research assistants at our institution for their invaluable support.
K. S., principal investigator, received a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (grant number 18K08912).
Availability of data and materials: Data analyzed in this study are available from the corresponding author upon reasonable request.
The authors declare no conflict of interest in relation to this study.
Sensitivity and specificity of the Confusion assessment method for the intensive care Unit (CAM-ICU) and the intensive care delirium screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: a single-center study in Japan.
Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development.
Clinical practice guidelines for the prevention and management of pain, agitation/Sedation, delirium, Immobility, and sleep disruption in adult patients in the ICU.
Changing pattern of agitated impaired mental status in patients with advanced cancer: association with cognitive monitoring, hydration, and opioid rotation.
Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study.
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