Temperature Profile and Adverse Outcomes After Discharge From the Intensive Care Unit

Rob Boots, PhD, MBBS, MHAIT; Gabrielle Mead, BSci(Hon); Oliver Rawashdeh, PhD, MSci; Judith Bellapart, PhD, MBChB; Shane Townsend, MBBS, MBA; Jenny Paratz, PhD, MPthy; Nicholas Garner, BSci (Hon); Pierre Clement, DipHSc(Nursing), GCert(Critical Care), BIT; David Oddy, BNursing, GCert(Critical Care), DipIT

Disclosures

Am J Crit Care. 2022;31(1):e1-e9.

Abstract and Introduction

Abstract

Background: A predictive model that uses the rhythmicity of core body temperature (CBT) could be an easily accessible clinical tool to ultimately improve outcomes among critically ill patients.

Objectives: To assess the relation between the 24-hour CBT profile (CBT-24) before intensive care unit (ICU) discharge and clinical events in the step-down unit within 7 days of ICU discharge.

Methods: This retrospective cohort study in a tertiary ICU at a single center included adult patients requiring acute invasive ventilation for more than 48 hours and assessed major clinical adverse events (MCAEs) and rapid response system activations (RRSAs) within 7 days of ICU discharge (MCAE-7 and RRSA-7, respectively).

Results:The 291 enrolled patients had a median mechanical ventilation duration of 139 hours (IQR, 50–862 hours) and at admission had a median Acute Physiology and Chronic Health Evaluation II score of 22 (IQR, 7–42). At least 1 MCAE or RRSA occurred in 64% and 22% of patients, respectively. Independent predictors of an MCAE-7 were absence of CBT-24 rhythmicity (odds ratio, 1.78 [95% CI, 1.07–2.98]; P = .03), Sequential Organ Failure Assessment score at ICU discharge (1.10 [1.00–1.21]; P = .05), male sex (1.72 [1.04–2.86]; P = .04), age (1.02 [1.00–1.04]; P = .02), and Charlson Comorbidity Index (0.87 [0.76–0.99]; P = .03). Age (1.03 [1.01–1.05]; P = .006), sepsis at ICU admission (2.02 [1.13–3.63]; P = .02), and Charlson Comorbidity Index (1.18 [1.02–1.36]; P = .02) were independent predictors of an RRSA-7.

Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

Table 1. Demographic characteristics of 291 patients in the study
Variable^a	Value^a
Age, y	57 (19–82), 18–90
Male sex	188 (64.6)
ICU length of stay, d	8 (2–43), 2–51
Hospital length of stay, d	26.7 (4.9–105.9), 3.7–137.1
Admission type
Medical	212 (72.9)
Surgical	25 (8.6)
Trauma	54 (18.6)
Sepsis as part of ICU primary admission	119 (40.9)
Acute renal failure	40 (13.8)
Charlson Comorbidity Index	2 (0–8), 0–10
Comorbidities
None	1 (0.3)
1	144 (49.5)
2	55 (18.9)
3	50 (17.2)
4	28 (9.6)
5	6 (2.1)
6	6 (2.1)
7	1 (0.3)
SOFA score
ICU admission	11 (2–19), 0–20
ICU discharge	4 (0–12), 0–14
APACHE II score
ICU admission	22 (7–42), 4–45
ICU discharge	13 (2–27), 0–40
APACHE III score at ICU admission	68 (25–148), 21–161
APACHE II chronic health categories (n = 289 patients)
Renal	8 (2.8)
Cardiovascular	3 (1.0)
Respiratory	6 (2.1)
Immunocompromised	12 (4.1)
Liver	13 (4.5)
Nonoperative or emergency postoperative patients.	289 (100.0)
Duration of invasive ventilation, h	139 (50–862), 49–1211
Duration of sedation, h	119 (11–566), 0–826
Duration of noninvasive ventilation, h (n = 89)	7 (1–82), 1–137
Duration of continuous dialysis, h (n = 60)	120.5 (27–369), 5–745
Duration of inotropic therapy, h (n = 208)	49.5 (2–342), 1–541
Duration of Ileus, h (n = 73)	118 (16–450), 2–875
Sedation and analgesia drug use 24 hours before discharge
Antidepressants	25 (8.6)
Benzodiazepines	67 (23.0)
Major tranquilizers	52 (17.9)
Narcotic sedatives (including α₂-agonists) α₂-Agonists	132 (45.4) 52 (17.9)
Patients' hospital outcomes
Survived ICU, died in hospital	25 (8.6)
Died in ICU (upon readmission to ICU)	1 (0.3)
Transferred to chronic care or rehabilitation	75 (25.8)
Transferred to another acute care hospital	39 (13.4)
Discharged home	151 (51.9)

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, intensive care unit; IQR, interquartile range; SOFA, Sequential Organ Failure Assessment.
^aUnless otherwise indicated, data are No. (%) of patients or median (IQR), range.

Table 2. Summary of characteristics of rapid response system activations among 291 study patients
Parameter	Value^a
Total No. of RRSA events	100
Patients requiring at least 1 RRSA	64 (22.0)
No. of RRSA events per patient
0	229 (78.7)
1	45 (15.5)
2	10 (3.4)
3	4 (1.4)
4	3 (1.0)
5	1 (0.3)
6	1 (0.3)
Time to RRSA following ICU discharge, d (n = 100 events)	4.5 (0–42), 0–57
RRSA within 7 days of ICU discharge	62 (62.0)
RRSA within 14 days of ICU discharge	80 (80.0)
APACHE II score at time of RRSA (n = 100 events)	15 (7–33), 6–40
SOFA score at time of RRSA (n = 100 events)	5 (0–11), 0–13
RRS-A event criteria
Cardiac arrest	3 (3.0)
Threatened airway	6 (6.0)
Breathing difficulty	73 (73.0)
Neurologic disturbance	37 (37.0)
Pain	8 (8.0)
Sepsis	11 (11.0)
Delirium on day of RRSA	39 (39.0)
RRS-A event outcome
Died within 24 hours of RRSA	3 (3.0)
Remained in general care area	82 (82.0)
Transferred to ICU	15 (15.0)
Palliation
Commenced after RRSA event	7 (7.0)
Palliated already at time of RRSA event	3 (3.0)

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, intensive care unit; IQR, interquartile range; RRS-A, rapid response team activation; SOFA, Sequential Organ Failure Assessment.
^aData are median (IQR), range or No. (%) among 100 events, unless otherwise indicated.

Table 3. Summary of clinical event characteristics for 291 patients in the study
Characteristic	Value
No. (%) of patients with clinical events	192 (66.0)
Total No. of clinical events	597
No. of clinical events per patient, No. (%) of 291 patients
0	99 (34.0)
1	77 (26.5)
2	50 (17.2)
3	32 (11.0)
4	7 (2.4)
5	8 (2.8)
>5 In those who had at least 1 clinical event	18 (6.2)
No. of clinical events per patient, median (IQR), range	2 (1–16), 1–66
Time to clinical event after ICU discharge, median (IQR), range, d	6 (0–103), 0–115
Clinical events <7 days after ICU, No. (%) of 597 events	300 (50.3)
Clinical events <14 days after ICU, No. (%) of 597 events	401 (67.2)
Categorization of event, No. (%) of 597 events
Cardiovascular	53 (8.9)
Neurological	144 (24.1)
Gastrointestinal	16 (2.7)
Renal	23 (3.9)
Respiratory	25 (4.2)
Sepsis	113 (18.9)
Blood/blood products	209 (35.0)
Other	24 (4.0)
Clinical event episodes included in major event,
No. (%) of 597 events
Delirium	131 (21.9)
Pneumonia	40 (6.7)
Deep venous thrombosis/pulmonary thromboembolism	40 (6.7)
Urinary tract infection	3 (0.5)
Myocardial infarction	1 (0.2)
New-onset arrhythmia	4 (0.7)
Catheter-related bloodstream infection	8 (1.3)
Patients with at least 1 major clinical adverse event	185 (63.6)
No. of major clinical events per patient (n = 185), median (IQR), range	2 (1–8), 1–43

Abbreviations: ICU, intensive care unit; IQR, interquartile range.

Table 4. Univariate and multivariate logistic regression models for rapid response system activation within 7 days of ICU discharge ^a
Logistic regression model	Odds ratio (95% CI)	P
Univariate
Age, y	1.04 (1.02–1.06)	.001
Male sex (reference: female sex)	0.75 (0.42–1.33)	.32
Sepsis diagnosis at ICU admission	2.01 (1.17–3.60)	.01
APACHE II score
ICU admission	1.05 (1.01–1.08)	.01
ICU discharge	1.07 (1.02–1.13)	.01
Core temperature not rhythmic at ICU discharge	1.58 (0.97–2.58)	.06
ICU length of stay, d	1.02 (0.99–1.05)	.16
Duration, d
Invasive ventilation	1.00 (0.99–1.00)	.35
Inotropic therapy	1.00 (1.00–1.00)	.47
Ileus	1.00 (1.00–1.00)	.16
Continuous dialysis	1.00 (0.99–1.01)	.06
Sedation	1.00 (1.00–1.00)	.86
Acute renal failure diagnosis at ICU admission	1.64 (0.78–3.44)	.19
APACHE II chronic health conditions^b
Renal	2.18 (0.51–9.39)	.29
Respiratory	0.70 (0.08–6.14)	.75
Immunocompromised	1.19 (0.31–4.54)	.80
Liver	0.28 (0.04–2.23)	.23
Nonoperative or emergency postoperative patients	0.28 (0.02–4.52)	.37
APACHE III score at ICU admission	1.01 (1.01–1.02)	.002
SOFA score
At ICU admission	1.07 (1.00–1.15)	.08
At ICU discharge	1.14 (1.03–1.27)	.02
Charlson Comorbidity Index
Count	1.00 (1.00–1.00)	.77
Sum	1.25 (1.09–1.43)	.001
Type of ICU admission (reference: medical)
Surgical	1.05 (0.40–2.78)	.92
Trauma	0.66 (0.30–1.46)	.31
Multivariate^c
Charlson Comorbidity Index	1.18 (1.02–1.36)	.02
Age, y	1.03 (1.01–1.05)	.006
Sepsis at ICU admission	2.02 (1.13–3.63)	.02

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment.
^aLikelihood ratio χ² = 24.09, P < .001. Hosmer-Lemeshow goodness of fit χ² = 10.57, P = .23. Area under receiver operating characteristic curve = 0.70.
^bCardiovascular completely predicted rapid response system activation within 7 days of ICU discharge.
^cStepwise forward inclusion of univariate associations where P < .25.

Table 5. Univariate and multivariate logistic regression models for major clinical adverse events within 7 days of ICU discharge ^a
Logistic regression model	Logistic regression model	P
Univariate
Age, y	1.02 (1.00–1.03)	.03
Male (reference: female sex)	1.62 (1.00–2.64)	.05
Sepsis diagnosis at ICU admission	0.71 (0.44–1.13)	.15
APACHE II score
ICU admission	1.02 (0.99–1.04)	.29
ICU discharge	1.04 (0.34–1.17)	.10
Core temperature not rhythmic at ICU discharge	1.58 (0.97–2.58)	.06
ICU length of stay, d	1.03 (1.00–1.04)	.05
Duration, d
Inotrope therapy	1.00 (1.00–1.00)	.07
Invasive mechanical ventilation	1.00 (1.00–1.00)	.05
Ileus	1.00 (0.99–1.00)	.86
Continuous dialysis	1.00 (0.99–1.00)	.88
Acute renal failure diagnosis at ICU admission	0.98 (0.50–1.90)	.94
APACHE II chronic health conditions
Renal	1.65 (0.39–7.06)	.50
Cardiovascular	1.97 (0.18–22.00)	.58
Respiratory	0.98 (0.19–4.93)	.98
Immunocompromised	0.48 (0.14–1.62)	.23
Liver	0.83 (0.27–2.54)	.75
Nonoperative or emergency postoperative patients	1.02 (0.06–16.48)	.99
APACHE III score on ICU admission	1.02 (1.00–1.01)	.20
SOFA score
ICU admission	1.01 (0.95–1.07)	.75
ICU discharge	1.10 (1.00–1.21)	.05
Charlson Comorbidity Index
Count	0.97 (0.81–1.16)	.75
Sum	0.93 (0.83–1.05)	.24
Type of ICU admission (reference: medical)
Surgical	0.57 (0.24–1.35)	.21
Trauma	1.60 (0.87–2.95)	.13
Multivariate^b
Core temperature not rhythmic at ICU discharge	1.78 (1.07–2.98)	.03
Charlson Comorbidity Index	0.87 (0.76–0.99)	.03
Age, y	1.02 (1.00–1.04)	.02
Male sex	1.72 (1.04–2.86)	.04
SOFA score at ICU discharge	1.10 (1.00–1.21)	.05

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment.
^aLikelihood ratio χ² = 20.93, P < .002. Hosmer-Lemeshow goodness of fit χ² = 2.74, P = .95. Area under receiver operating characteristic curve = 0.65.
^bStepwise forward inclusion of univariate associations when P < .25.

Supplemental Table 1. Onset of clinical adverse events in general care areas after discharge from the intensive care unit ²⁵
Nosocomial Infection of a defined organ system, wound or catheter related, requiring antibiotic therapy (ICD-10 clinical code)
Myocardial infarction both ST elevation and non-ST elevation/ischemia/arrhythmia, either supraventricular or ventricular, requiring clinical treatment (ICD-10 clinical code)
Deep venous thrombosis/pulmonary thromboembolism proven by radiology and requiring treatment (ICD-10 clinical code)
Confusion/delirium assessed through bedside nursing assessment of level of consciousness
Insulin therapy for blood glucose control in a patient with previously unknown diabetes
Peak alkaline transaminase and total bilirubin levels on routine biochemical assessment to document the presence of potential hepatic dysfunction
Ileus defined as a clinical description of abdominal distension, need for nasogastric drainage and cessation of enteral feedings
Hyponatremia (sodium ≤130 mmol/L)
Worsening estimated glomerular filtration rate
Need for blood transfusion

Abbreviation: ICD-10, International Statistical Classification of Diseases, Tenth Revision.

Supplemental Table 2. Drug classes prescribed per patient within 24 hours of discharge from the intensive care unit
Drug class	No. (%) of 291 patients
Angiotensin-converting enzyme/aII inhibitors	22 (7.6)
Antiarrhythmics	12 (4.1)
Antibiotics	185 (63.6)
Anticoagulants	236 (81.1)
Anticonvulsants	46 (15.8)
Antidepressants	26 (8.9)
Antiemetics	44 (15.1)
Antihypertensives	43 (14.8)
Benzodiazepines	67 (23.0)
β-Blockers	64 (22.0)
Bronchodilators	109 (37.5)
Diabetes medications	72 (24.7)
Diuretics	89 (30.6)
Digoxin	12 (4.1)
Fluids	128 (44.0)
H₂ antagonists	33 (11.3)
Inhaled corticosteroids	40 (13.7)
Lipid-lowering drugs	22 (7.6)
Major tranquilizers	52 (17.9)
Narcotics	132 (45.4)
Nonsteroidal anti-inflammatory drugs/Cox-2	42 (14.4)
Other immunosuppressants	7 (2.4)
Other medications	195 (67.0)
Acetaminophen	175 (60.1)
Prescribed nutrition	159 (54.6)
Proton pump inhibitors	160 (55.0)
Sedatives	58 (19.9)
Systemic corticosteroids	65 (22.3)

Supplemental Table 3. Summary of Charlson comorbidities
Charlson comorbidity	No. (%) of 291 patients
Cardiovascular
Hypertension	98 (33.7)
Respiratory
Pulmonary disease/asthma	70 (24.1)
None	64 (22.0)
Mood
Depression	63 (21.6)
Mood
Other psychiatric disease	48 (16.5)
Endocrine
Diabetes mellitus (no end-organ disease)	43 (14.8)
Cardiovascular
Congestive heart failure	28 (9.7)
Cancer
Nonmetastatic (solid organ)	22 (7.6)
Gastroenterology
Liver disease (mild)	21 (7.2)
Cardiovascular
Cerebrovascular disease/transient ischemic attack	19 (6.5)
Gastroenterology
Liver disease (moderate/severe)	17 (5.8)
Hematology
Anticoagulation: warfarin/novel oral anticoagulants	16 (5.5)
Hematology
Anticoagulation: platelet IIa/IIIb inhibitors	14 (4.8)
Renal
Moderate/severe renal disease	13 (4.5)
Cancer
Leukemia	9 (3.1)
Gastroenterology
Gastric/peptic ulcer	9 (3.1)
Cardiovascular
Peripheral vascular disease/bypass	8 (2.7)
Cardiovascular
Myocardial infarction	7 (2.4)
Endocrine
Diabetes mellitus (with end-organ disease)	7 (2.4)
Dermatology
Skin ulcers/cellulitis	6 (2.1)
Infectious
HIV/AIDS	3 (1.0)
Central nervous system
Hemiplegia	2 (0.7)
Cancer
Lymphoma	2 (0.7)

Supplemental Table 4 Temperature sources and frequency of use among 289 patients during their final 24 hours in the intensive care unit
Parameter	Median (IQR), range
No. of temperature measurements per patient	22 (11–24), 6–35
No. of temperature measurements per patient by site
Urinary bladder	23 (21–25), 1–35
Axillary	7 (2–8), 1–16
Nasopharyngeal	14 (7–19), 1–23
Tympanic	4 (1–9), 1–10
Esophageal	3 (3–10), 2–22
Oral	1 (1–1), 1–1
Blood	1 (1–1), 1–1
Rectal	1 (1–1), 1–1
Percentage of temperature measurements available per patient by site
Urinary bladder	100 (100–100), 10–100
Axillary	100 (13–100), 4–100
Nasopharyngeal	70 (37–87), 13–96
Tympanic	46 (17–100), 4–100
Esophageal	33 (25–56), 8–96
Oral	9 (5–13), 5–13
Blood	7 (5–8), 5–8
Rectal	2 (2–2), 2–2

Supplemental Table 5. Clinical events occurring in general care area after intensive care unit discharge
Clinical event	No. (%) of 597 events
Acute myocardial infarction	1 (0.2)
Acute dialysis	4 (0.7)
Acute kidney injury	17 (2.9)
Acute noninvasive ventilation	15 (2.5)
Anaphylaxis	1 (0.2)
Bloodstream infection	8 (1.3)
Deep venous thrombosis	28 (4.7)
Delirium	131 (21.9)
Dysrhythmia	4 (0.7)
Exacerbation of airway disease	1 (0.2)
Gastrointestinal obstruction/ileus	9 (1.5)
Gastrointestinal infection	6 (1.0)
New insulin therapy (no diabetes previously)	7 (1.2)
New-onset liver dysfunction	1 (0.2)
Pneumonia	40 (6.7)
Pulmonary emboli	12 (2.0)
Red blood cell transfusion	144 (24.1)
Seizure	3 (0.5)
Soft-tissue infection	18 (3.0)
Stroke	3 (0.5)
Urinary tract infection	31 (5.2)
Other events
Platelet transfusion	61 (10.2)
Other blood product transfusion	4 (0.7)
Event categories
Neurological	144 (24.1)
Renal	23 (3.9)
Respiratory	25 (4.2)
Sepsis	113 (18.9)
Gastrointestinal	16 (2.7)
Cardiovascular	53 (8.9)

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Temperature Profile and Adverse Outcomes After Discharge From the Intensive Care Unit

Abstract and Introduction

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