Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study *

Abstract

Background

Hypotension with endotracheal intubation (ETI) is common and associated with adverse outcomes. We sought to evaluate whether a previously described hypotension prediction score (HYPS) for ETI is associated with worse patient outcomes and/or clinical conditions.

Methods

This study is a post hoc analysis of a prospective observational multicenter study involving adult (age ≥18 years) intensive care unit (ICU) patients undergoing ETI in which the HYPS was derived and validated on the entire cohort and a stable subset (ie, patients in stable condition). We evaluated the association between increasing HYPSs in both subsets and several patient-centered outcomes and clinical conditions.

Results

Complete data for HYPS calculations were available for 783 of 934 patients (84%). Logistic regression analysis showed increasing odds ratios (ORs) for the highest risk category for new-onset acute kidney injury (OR, 7.37; 95% CI, 2.58-21.08); new dialysis need (OR, 8.13; 95% CI, 1.74-37.91); ICU mortality (OR, 16.39; 95% CI, 5.99-44.87); and hospital mortality (OR, 18.65; 95% CI, 6.81-51.11). Although not increasing progressively, the OR for the highest risk group was significantly associated with new-onset hypovolemic shock (OR, 6.06; 95% CI, 1.47-25.00). With increasing HYPSs, median values (interquartile ranges) decreased progressively (lowest risk vs. highest risk) for ventilator-free days (23 [18-26] vs. 1 [0-21], P < .001) and ICU-free days (20 [11-24] vs. 0 [0-13], P < .001). Of the 729 patients in the stable subset, 598 (82%) had complete data for HYPS calculations. Logistic regression analysis showed significantly increasing ORs for the highest risk category for new-onset hypovolemic shock (OR, 7.41; 95% CI, 2.06-26.62); ICU mortality (OR, 5.08; 95% CI, 1.87-13.85); and hospital mortality (OR, 7.08; 95% CI, 2.63-19.07).

Conclusions

As the risk for peri-intubation hypotension increases, according to a validated hypotension prediction tool, so does the risk for adverse clinical events and certain clinical conditions.

Trial Registration

The study was registered at ClinicalTrials.gov (NCT02508948).

Keywords

endotracheal intubation hypotension mortality outcomes prognosis scoring systems

Background

Unlike endotracheal intubation (ETI) in the operating room, ETI in a non–operating room environment is frequently associated with morbidity and mortality.^1–4 For example, the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society conducted a 1-year review of all National Health Service hospitals in the UK and found that the risk of major morbidity and mortality was 58-fold higher for emergency airway management compared to elective airway management.⁴ Moreover, the incidence of cardiovascular derangements such as hypotension has been reported to be 30% or higher for ICU patients.^5–7 Hypotensive episodes in critically ill patients are associated with increased morbidity and mortality.^8–10 Maheshwari et al.⁸ demonstrated that for every 1-unit increase in time-weighted average mean arterial pressure (MAP) less than 65 mm Hg, the odds of in-hospital death increased 11.4%, the odds of acute kidney injury (AKI) increased 7.0%, and the odds of myocardial injury increased 4.5%. Postoperative hypotension in surgical ICU patients was found to be associated with a statistically significant increase in the risk of myocardial injury and mortality at pressures previously thought to be normal (MAP 65-70 mm Hg).¹¹ Furthermore, after noncardiac surgery in patients who did not have intraoperative hypotension, postoperative hypotension (MAP <65 mm Hg) in the ICU was associated with major adverse cardiac or cerebrovascular events (hazard ratio [HR], 1.52; 98.4% CI, 1.17-1.96); 30-day mortality (HR, 1.56; 98.4% CI, 1.22-2.00); and 90-day mortality (HR, 1.49; 98.4% CI, 1.20-1.87).¹²

Although evidence suggests that ETIs performed in emergent settings such as the ICU are associated with a higher rate of complications (eg, hypotension, hypoxia), and that these complications result in greater morbidity and mortality, there is no evidence to the authors’ knowledge that demonstrates an association with hypotension occurring during ETI and clinical conditions. Studies do suggest an association with shock index and peri-intubation hypotension, but fail to identify specific shock states.^13,14 In addition, there is no evidence to the authors’ knowledge evaluating a hypotension prediction tool in ICU patients and adverse events such as organ failure or death.

Previously, in our large prospective multicenter ICU study of airway management among critically ill patients needing ETI, we derived and validated a hypotension prediction score (HYPS) for an entire ICU cohort (full cohort) and a “stable” version ([s]HYPS) for a subset of patients in stable condition (stable cohort – those who were not receiving catecholamine vasopressors pre-intubation and/or who were not intubated in the setting of cardiac arrest) (Appendix 2).⁵ We identified several variables in the full cohort and in the stable cohort that, when combined into a scoring system, could be used to reasonably predict hypotension after ETI (MAP <65 mm Hg, systolic blood pressure <80 mm Hg, and vasoactive agent requirement) with increasing severity. With evidence that indicates an association between hypotension in the critically ill and adverse outcomes, we sought to evaluate whether the HYPS and the (s)HYPS were associated with adverse clinical outcomes (such as need for tracheostomy or new dialysis, new-onset acute kidney injury, ICU-free days, ventilator-free days, ICU mortality, and hospital mortality) or clinical conditions (such as new-onset sepsis and hypovolemic shock) among critically ill patients undergoing ETI.

Methods

Study Approval

The study was originally approved by the Mayo Clinic Institutional Review Board (No. 15-002328), which served as the primary regulatory body, and by the institutional review boards of the participating centers. The study was registered at ClinicalTrials.gov (NCT02508948; Registered Report Identifier, RR2-10.2196/11101).

Study Population and Design

This study, a post hoc analysis of a multicenter, prospective, observational study of critically ill adult patients (age ≥18 years) who required ETI during their ICU stay, included 16 ICUs in 7 Health and Human Services regions around the US.⁵ Patients were excluded if ETI occurred in non-ICU environments, if blood pressure data from before and after intubation were not available, or if their center had no more than 5 enrollments.

The study used a predefined case report form in which data were entered prospectively.⁵ Follow-up data were recorded at hospital discharge; data were entered into a central data repository and data quality checks were performed at the conclusion of the study. The intubation process was not standardized, but ETI was performed according to each institution's policy. The study defined peri-intubation hypotension as any recorded MAP less than 65 mm Hg, any recorded systolic blood pressure less than 80 mm Hg or a decrease from baseline of at least 40%, or the initiation or increase of any vasoactive agent in the 30 minutes after ETI with the baseline blood pressure recorded closest to ETI. The following 11 variables for the full cohort were independently associated with peri-intubation hypotension: Acute Physiology and Chronic Health Evaluation (APACHE) II score; age; sepsis diagnosis; intubation within the context of cardiovascular collapse, MAP less than 65 mm Hg, or acute respiratory failure; diuretic use 24 hours before intubation; catecholamine or phenylephrine use immediately before intubation; preintubation systolic blood pressure; and etomidate use during intubation. Patients in the full cohort were then classified into quartiles according to their risk for hypotension with reasonably good calibration (low ≤19%; moderate, 20%-39%; high, 40%-59%; and very high, ≥60%). Similarly, a sensitivity analysis was done for the stable cohort, for patients who were not receiving preintubation catecholamine vasopressors, patients who were intubated because of cardiac arrest, and patients undergoing ETI. The following variables were used: APACHE II score; age; intubation because of MAP less than 65 mm Hg or acute respiratory failure; diuretic use 24 hours before intubation; phenylephrine use immediately before intubation; preintubation systolic blood pressure; and etomidate use during intubation. These patients were reclassified into 3 categories according to their risk for hypotension with reasonably good calibration (low ≤19%; moderate, 20%-39%; and high, ≥40%).⁵

Study Outcome

The current post hoc analysis evaluated the association between the HYPS and (s)HYPS tools and 1) adverse clinical events such as need for tracheostomy or new dialysis, new-onset acute kidney injury, ICU-free days, mechanical ventilation–free days, ICU mortality, and hospital mortality; and 2) clinical conditions such as new-onset sepsis and hypovolemic shock.

Statistical Analysis

Patient and procedural characteristics are presented overall and according to HYPS risk categorization as mean (SD) or median (25th and 75th quartiles) for continuous variables and as frequency counts and percentages for categorical variables. In an analysis restricted to patients who had complete data available for calculating the HYPS, binary outcomes/conditions were compared across HYPS risk categories with theχ² test, and continuous outcomes were compared across categories with the Kruskal-Wallis test. Additional analyses were performed with all patients, including those with missing data for variables required for calculation of the HYPS. To account for missing data for variables required for the HYPS, the analyses based on all patients were performed with 20 imputed data sets, which were created with fully conditional specification methods. Binary outcomes/conditions were analyzed with logistic regression, and results were combined according to the Rubin rules. All analyses were repeated for the stable cohort with the (s)HYPS as the explanatory variable of interest to evaluate how robust the finding are as a sensitivity analysis. In all analyses, 2-tailed P values less than .05 were considered statistically significant.

Results

Patient Characteristics

Overall, 934 patients in the full cohort were included in the analysis after exclusion of 354 patients because they had incomplete baseline data, they did not have blood pressure data from measurements before and after intubation, or they were from centers with no more than 5 enrollments. After an additional 151 patients were excluded for missing HYPS risk data because an APACHE II score was not available, 783 patients remained.

Sensitivity analysis was conducted for the 729 patients in the stable cohort from our prior publication, and then 131 patients were excluded for missing HYPS risk data because an APACHE II score was not available, so that 598 patients remained in the stable cohort (Figure 1).

Of the 934 patients in the full cohort, 534 (57%) were male; the mean age (SD) was 62.4 (15.6) years, and the mean APACHE II score was 17.5 (8.3). The most common indication for intubation was acute respiratory failure (686 patients; 73%) with over half the intubations described as emergent (508; 54%). Tables 1 and 2 present additional baseline characteristics of the full cohort and of the 783 patients with data for HYPS risk.

Table 1.

Patient Characteristics for Full Cohort.

		HYPS risk category (N = 783^*)
Characteristic	Overall (N = 934^*)	Low ≤1.5 (N = 81)	Moderate 2.0 to 10.5 (N = -434)	High 11.0 to 18.5 (N = 179)	Very High ≥19.0 (N = 89)
Age (years), mean ± standard deviation	62.4 ± 15.6	49.3 ± 14.8	62.7 ± 15.0	66.9 ± 14.8	66.8 ± 13.1
Sex, n (%)
Male	534 (57.2)	55 (67.9)	253 (58.3)	99 (55.3)	41 (46.1)
Female	400 (43.8)	26 (32.1)	181 (41.7)	80 (44.7)	48 (53.9)
Body mass index, kilogram/meter²	29.4 ± 9.1	29.0 ± 7.5	28.8 ± 8.7	29.4 ± 9.7	31.3 ± 11.1
Medical history, n (%)
Previous difficult endotracheal intubation	13 (1.4)	1 (1.2)	9 (2.1)	2 (1.1)	0 (0.0)
Congestive heart failure	198 (21.2)	7 (8.6)	81 (18.7)	61 (34.1)	23 (25.8)
Coronary artery disease	244 (26.1)	13 (16.1)	112 (25.8)	62 (34.6)	25 (28.1)
Obstructive lung disease	199 (21.3)	16 (19.8)	109 (25.1)	33 (18.4)	12 (13.5)
End-stage renal disease	72 (7.7)	3 (3.7)	28 (6.5)	18 (10.1)	13 (14.6)
Cirrhosis	105 (11.2)	3 (3.7)	45 (10.4)	24 (13.4)	17 (19.1)
Diabetes mellitus type 2	278 (29.8)	15 (18.5)	132 (30.4)	59 (33.0)	32 (36.0)
Acute kidney injury stage 1 or higher (AKIN or RIFLE)	322 (34.5)	11 (13.6)	140 (32.3)	87 (48.6)	48 (53.9)
Dialysis or renal replacement therapy	64 (6.9)	3 (3.7)	27 (6.2)	18 (10.1)	12 (13.5)
Mechanical circulatory support (VAD, IABP, ECMO)	19 (2.0)	0 (0.0)	6 (1.4)	3 (1.7)	6 (6.7)
Sepsis-3 (2016)	386 (41.3)	18 (22.2)	159 (36.6)	100 (55.9)	55 (61.8)
Hypovolemic shock^†	123 (13.2)	3 (3.7)	28 (6.5)	36 (20.1)	36 (40.5)
Emergency intubation, n (%)	508 (54.4)	43 (53.1)	250 (57.6)	101 (56.4)	58 (65.2)
Intubation setting, n (%)
Airway protection	600 (64.2)	55 (67.9)	279 (64.3)	113 (63.1)	59 (66.3)
Acute respiratory failure	686 (73.5)	45 (55.6)	341 (78.6)	139 (77.7)	67 (75.3)
Neurologic	217 (23.2)	19 (23.5)	105 (24.2)	40 (22.4)	16 (18.0)
Cardiac arrest	39 (4.2)	0 (0.0)	12 (2.8)	11 (6.2)	11 (12.4)
MAP < 65 mm Hg - hemodynamic decompensation	175 (18.7)	0 (0.0)	23 (5.3)	66 (36.9)	61 (68.5)
Procedural-related	146 (15.6)	15 (18.5)	64 (14.8)	18 (10.1)	7 (7.9)

^†

Hypovolemic shock: critical decrease in intravascular volume leading to inadequate perfusion (as measured by decreased urine output or increased lactate) resulting in imbalance between oxygen supply/demand.

HYPS: hypotension prediction score; AKIN: acute kidney injury network; RIFLE: risk, injury, failure, loss of kidney function and end-stage kidney disease; VAD: ventricular assist device; IABP: intra-aortic balloon pump; ECMO: extracorporeal membrane oxygenation; MAP: mean arterial pressure.

Table 2.

Peri-Intubation Characteristics for Patients in Full Cohort.

	HYPS risk category (N = 783^*)
Characteristic	Overall (N = 934^*)	Low ≤1.5 (N = 81)	Moderate 2.0 to 10.5 (N = -434)	High 11.0 to 18.5 (N = 179)	Very High ≥19.0 (N = 89)
24 hours prior to endotracheal intubation
APACHE II score, mean ± SD	17.5 ± 8.3	8.8 ± 3.6	16.6 ± 7.1	20.7 ± 8.5	23.3 ± 8.7
Cardiovascular medications, n (%)
Diuretics	154 (16.5)	0 (0.0)	71 (16.4)	51 (28.5)	21 (23.6)
Alpha blocker	11 (1.2)	1 (1.2)	5 (1.2)	4 (2.2)	1 (1.1)
Beta blocker	97 (10.4)	12 (14.8)	56 (12.9)	16 (8.9)	7 (7.9)
Ace inhibitors	3 (0.3)	0 (0.0)	3 (0.7)	0 (0.0)	0 (0.00)
Midodrine	14 (1.5)	0 (0.0)	4 (0.9)	7 (3.9)	3 (3.4)
Calcium channel blocker	63 (6.8)	4 (4.9)	40 (9.2)	7 (3.9)	4 (4.5)
Nitrates	28 (3.0)	4 (4.9)	17 (3.9)	7 (3.9)	0 (0.0)
Anti-arrhythmic	90 (9.6)	4 (4.9)	44 (10.1)	20 (11.2)	14 (15.7)
Fluid balance (milliliters), mean ± SD	+ 522 ± 2153	+ 108 ± 1608	+ 226 ± 1947	+ 595 ± 2112	+ 2326 ± 2626
Non-invasive ventilation	282 (30.2)	15 (18.5)	140 (32.3)	65 (36.3)	25 (28.1)
High flow nasal cannula	36 (3.9)	0 (0.0)	16 (3.7)	11 (6.2)	2 (2.3)
Vasopressors
Calcium	13 (1.4)	0 (0.0)	1 (0.2)	5 (2.8)	5 (5.6)
Catecholamine	179 (19.2)	0 (0.0)	26 (6.0)	62 (34.6)	77 (86.5)
Vasopressin	45 (4.8)	0 (0.0)	2 (0.5)	15 (8.4)	21 (23.6)
Phenylephrine	51 (5.5)	1 (1.2)	10 (2.3)	21 (11.7)	10 (11.2)
Inotrope (dobutamine or milrinone)	19 (2.0)	0 (0.0)	4 (0.9)	7 (3.9)	4 (4.5)
Lactate (mmol/L), median (IQR)	1.6 (0.8, 3.1)	1.0 (0.6, 1.9)	1.4 (0.6, 2.4)	2.0 (1.1, 4.2)	3.3 (1.1, 6.38)
SpO₂ (%), mean ± SD	94.7 ± 6.5	94.9 ± 6.1	94.9 ± 6.1	94.3 ± 7.2	94.1 ± 8.4
Systolic blood pressure (mm Hg), mean ± SD	123.8 ± 31.3	150.8 ± 25.9	135.4 ± 26.6	104.3 ± 21.4	83.4 ± 13.8
Diastolic blood pressure (mm Hg), mean ± SD	68.6 ± 21.3	82.4 ± 16.2	73.3 ± 20.9	57.8 ± 15.5	49.0 ± 11.9
Mean arterial pressure (mm Hg), mean ± SD	87.0 ± 22.5	105.2 ± 16.4	94.0 ± 20.1	73.3 ± 15.6	60.7 ± 11.2
Ketamine	145 (15.5)	2 (2.5)	67 (15.4)	35 (19.6)	27 (30.3)
Propofol	240 (25.7)	18 (22.2)	141 (32.5)	38 (21.2)	12 (13.5)
Etomidate	504 (54.0)	63 (77.8)	214 (49.3)	94 (52.5)	38 (42.7)
Opioids	335 (35.9)	20 (24.7)	165 (38.0)	61 (34.1)	35 (39.3)
Benzodiazepines	299 (32.0)	15 (18.5)	124 (28.6)	50 (27.9)	28 (31.5)
Paralytic: depolarizing	258 (27.6)	33 (40.7)	126 (29.0)	55 (30.7)	18 (20.2)
Paralytic: non-depolarizing	394 (42.2)	32 (39.5)	186 (42.9)	56 (31.3)	40 (44.9)

Tidal volume (milliliter), mean ± SD	443 ± 78	456 ± 80	443 ± 75	443 ± 76	434 ± 66
Positive end-expiratory pressure (mm Hg), mean ± SD	6.51 ± 2.61	6.11 ± 2.55	6.41 ± 2.55	6.70 ± 2.65	6.57 ± 2.49

Of the 934 patients, there were 151 patients who had missing data for HYSP risk due to missing APACHE-II score. For the characteristics presented in the table, data were available for > 98% of patients for all characteristics except SpO₂, fluid balance, APACHE II score and lactate which were missing for 6%, 12%, 16% and 29% of patients respectively.

HYPS: hypotension prediction score; APACHE: acute physiology and chronic health evaluation; SD: standard deviation; mmol/L: millimoles per liter; IQR: interquartile range; mm Hg: millimeters of mercury.

Most patients in the stable cohort were male (419; 58%). The mean age (SD) was 61.6 (15.8) years, and the mean (SD) APACHE II score was 16.7 (8.1). The most common indication for intubation was acute respiratory failure (539; 74%) with over half the intubations described as emergent (377; 52%). Tables 3 and 4 present additional baseline characteristics of the stable cohort and of the 598 patients with data for HYPS risk.

Table 3.

Patient Characteristics for Stable Cohort.

	(s)HYPS risk category (N = 598^*)
Characteristic	Overall (N = 729^*)	Low ≤1.0 (N = 68)	Moderate 1.5 to 11.5 (N = 473)	High ≥12.0 (N = 57)
Age (years), mean ± standard deviation	61.6 ± 15.8	40.9 ± 11.2	64.3 ± 14.2	68.1 ± 13.5
Sex, n (%)
Male	419 (57.5)	45 (66.2)	276 (58.4)	27 (47.4)
Female	310 (42.5)	23 (33.8)	197 (71.6)	30 (52.6)
Body mass index, kilogram/meter²	29.1 ± 8.6	29.9 ± 11.2	28.4 ± 7.9	30.2 ± 10.1
Medical history, n (%)
Previous difficult endotracheal intubation	12 (1.7)	1 (1.5)	9 (1.9)	1 (1.8)
Congestive heart failure	129 (17.7)	5 (7.4)	90 (19.0)	15 (26.3)
Coronary artery disease	185 (25.4)	8 (11.8)	127 (26.9)	20 (35.1)
Obstructive lung disease	171 (23.5)	10 (14.7)	126 (26.6)	11 (19.3)
End-stage renal disease	50 (6.7)	3 (4.4)	34 (7.2)	4 (7.0)
Cirrhosis	74 (10.2)	2 (2.9)	48 (10.2)	10 (17.5)
Diabetes mellitus type 2	215 (29.5)	12 (17.7)	140 (29.6)	26 (45.6)
Acute kidney injury stage 1 or higher (AKIN or RIFLE)	232 (31.8)	10 (14.7)	160 (33.8)	28 (49.1)
Dialysis or renal replacement therapy	39 (5.4)	2 (2.9)	30 (6.3)	4 (7.0)
Mechanical circulatory support (VAD, IABP, ECMO)	11 (1.5)	0 (0.0)	7 (1.5)	1 (1.8)
Sepsis-3 (2016)	272 (37.3)	19 (27.9)	182 (38.5)	28 (49.1)
Hypovolemic shock^†	63 (8.6)	3 (4.4)	36 (7.6)	10 (17.5)
Emergency intubation, n (%)	377 (51.7)	38 (55.9)	260 (55.0)	30 (52.6)
Intubation setting, n (%)
Airway protection	462 (63.4)	51 (75.0)	298 (63.0)	33 (57.9)
Acute respiratory failure	539 (73.9)	47 (69.1)	368 (77.8)	43 (75.4)
Neurologic	181 (24.8)	16 (23.5)	116 (24.5)	16 (28.1)
Cardiac arrest	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
MAP < 65 mm Hg - hemodynamic decompensation	78 (10.7)	0 (0.0)	40 (8.5)	20 (35.1)
Procedural-related	122 (16.7)	10 (14.7)	71 (15.0)	6 (10.5)

^†

(s)HYPS: stable hypotension prediction score; AKIN: acute kidney injury network; RIFLE: risk, injury, failure, loss of kidney function and end-stage kidney disease; VAD: ventricular assist device; IABP: intra-aortic balloon pump; ECMO: extracorporeal membrane oxygenation; MAP: mean arterial pressure.

Table 4.

Peri-Intubation Characteristics for Patients in Stable Cohort.

		(s)HYPS risk category (N = 598^*)
Characteristic	Overall (N = 729^*)	Low ≤1.0 (N = 68)	Moderate 1.5 to 11.5 (N = 473)	High ≥12.0 (N = 57)
24 hours prior to endotracheal intubation
APACHE II score, mean ± SD	16.7 ± 8.1	9.2 ± 3.9	17.3 ± 7.9	20.8 ± 8.2
Cardiovascular medications, n (%)
Diuretics	119 (16.3)	0 (0.0)	90 (19.0)	20 (35.1)
Alpha blocker	8 (1.1)	1 (1.5)	6 (1.3)	1 (1.8)
Beta blocker	83 (11.4)	9 (13.2)	61 (12.9)	8 (14.0)
Ace inhibitors	3 (0.4)	0 (0.0)	3 (0.6)	0 (0.0)
Midodrine	7 (1.0)	0 (0.0)	6 (1.3)	1 (1.8)
Calcium channel blocker	57 (7.8)	2 (2.9)	43 (9.1)	5 (8.8)
Nitrates	23 (3.2)	4 (5.9)	18 (3.8)	1 (1.8)
Anti-arrhythmic	64 (8.9)	2 (2.9)	47 (9.9)	7 (12.3)
Fluid balance (milliliters), mean ± SD	+ 224 ± 1867	+ 143 ± 2060	+ 228 ± 1811	+ 244 ± 1729
Non-invasive ventilation	223 (30.6)	12 (17.7)	159 (33.6)	18 (31.6)
High flow nasal cannula	31 (4.3)	1 (1.5)	19 (4.0)	5 (8.8)
Vasopressors
Calcium	4 (0.6)	1 (1.5)	1 (0.2)	1 (1.8)
Catecholamine	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Vasopressin	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Phenylephrine	34 (4.7)	0 (0.0)	17 (3.6)	10 (17.5)
Inotrope (dobutamine or milrinone)	7 (1.0)	0 (0.0)	3 (0.6)	3 (5.3)
Lactate (mmol/L), median (IQR)	1.5 (0.8, 2.7)	1.3 (0, 2.6)	1.4 (0.7, 2.5)	2.2 (1.5, 4.6)
SpO₂ (%), mean ± SD	94.8 ± 6.1	94.0 ± 6.7	94.9 ± 5.7	94.0 ± 9.0
Systolic blood pressure (mm Hg), mean ± SD	128.6 ± 30.2	152.0 ± 24.2	131.2 ± 27.6	84.2 ± 9.7
Diastolic blood pressure (mm Hg), mean ± SD	71.1 ± 21.4	84.6 ± 17.6	71.0 ± 20.5	50.0 ± 11.0
Mean arterial pressure (mm Hg), mean ± SD	90.3 ± 22.0	107.1 ± 17.1	91.1 ± 20.3	61.7 ± 9.3
Ketamine	97 (13.3)	3 (4.4)	72 (15.2)	10 (17.5)
Propofol	211 (28.9)	28 (41.2)	146 (30.9)	9 (15.8)
Etomidate	402 (55.1)	31 (45.6)	250 (52.9)	34 (59.7)
Opioids	267 (36.6))	18 (26.5)	179 (37.8)	23 (40.4)
Benzodiazepines	241 (33.1)	17 (25.0)	135 (28.5)	16 (28.1)
Paralytic: depolarizing	214 (29.4)	27 (39.7)	145 (30.7)	19 (33.3)
Paralytic: non-depolarizing	306 (42.0)	33 (48.5)	178 (37.6)	25 (43.9)
Tidal volume (milliliter), mean ± SD	442 ± 77	469 ± 82	439 ± 73	437 ± 61
Positive end-expiratory pressure (mm Hg), mean ± SD	6.46 ± 2.58	6.78 ± 2.94	6.37 ± 2.51	6.16 ± 1.86

Of the 729 stable patients, there were 131 patients who had missing data for HYSP risk due to missing APACHE-II score. For the characteristics presented in the table, data were available for > 98% of patients for all characteristics except SpO₂, fluid balance, APACHE II score and lactate which were missing for 6%, 14%, 18% and 35% of patients respectively.

(s)HYPS: stable hypotension prediction score; APACHE: acute physiology and chronic health evaluation; SD: standard deviation; mmol/L: millimoles per liter; IQR: interquartile range; mm Hg: millimeters of mercury.

Full Cohort Outcomes

Full cohort outcomes for new-onset AKI (P = .009), need for new dialysis (P < .001), new-onset sepsis (P = .04), new-onset hypovolemic shock (P < .001), ICU death (P < .001), and hospital death (P < .001) showed a statistically significant increase in a generally progressive manner with increasing risk for peri-intubation hypotension. Furthermore, ventilator-free days (P < .001) and ICU-free days (P < .001) significantly decreased in a progressive manner with increasing risk for peri-intubation hypotension (Table 5).

Table 5.

Outcomes Overall and According to HYPS Risk Categorization for Full Cohort.

HYPS risk category (N = 783^*)
	Overall		Low ≤1.5		Moderate 2.0 to 10.5		High 11.0 to 18.5		Very High ≥19.0
	(N = 934^*)		(N = 81)		(N = 434)		(N = 179)		(N = 89)
Characteristic	N^†	# (%)	N^†	# (%)	N^†	# (%)	N^†	# (%)	N^†	# (%)	P^‡
Tracheostomy	920	168 (18)	81	16 (20)	432	91 (21)	179	31 (17)	89	11 (12)	0.252
New-onset Acute Kidney Injury	586	113 (19)	68	6 (9)	287	51 (18)	84	19 (23)	34	14 (41)	0.009
New-onset Dialysis	870	62 (7)	78	2 (3)	407	19 (5)	161	15 (9)	77	12 (16)	<0.001
New-onset Sepsis	548	92 (17)	63	3 (5)	275	47 (17)	79	17 (22)	34	7 (21)	0.041
New-onset Hypovolemic Shock	811	92 (11)	78	2 (3)	406	39 (10)	143	33 (23)	53	8 (15)	<0.001
ICU death	934	232 (25)	81	4 (5)	434	85 (20)	179	65 (36)	89	46 (52)	<0.001
Hospital Death	934	257 (28)	81	4 (5)	434	97 (22)	179	75 (42)	89	49 (55)	<0.001
28-day outcomes
Ventilator-free days	920	21 (2, 25)	81	23 (18, 26)	432	22 (5, 26)	179	20 (0, 25)	89	1 (0, 21)	<0.001
ICU-free days	930	16 (0, 23)	81	20 (11, 24)	432	17 (0, 23)	179	13 (0, 23)	89	0 (0, 13)	<0.001

Of the 934 patients, there were 151 who had missing data for HYSP risk because an APACHE-II score was not available.

^†

Number of patients included for the analysis of the given outcome. For all outcomes, patients were excluded from the analysis if they had missing data for the outcome or if they were indicated to have the given condition prior to intubation.

^‡

Binary outcome variables are summarized using n (%) and compared across groups using the chi-square test. Ventilator-free days and ICU-free days are summarized using median (25^th, 75^th) and compared across groups using the Kruskal-Wallis test.

HYPS: hypotension prediction score; ICU: intensive care unit.

With the use of multiple imputation for missing characteristics, logistic regression analysis showed increasing odds ratios (ORs) for the outcomes of new-onset AKI (moderate risk: OR, 2.28; 95% CI, 0.98-5.31; high risk: OR, 2.98; 95% CI, 1.18-7.54; very high risk: OR, 7.37; 95% CI, 2.58-21.08); new dialysis need (moderate risk: OR, 2.73; 95% CI, 0.62-11.94; high risk: OR, 4.99; 95% CI, 1.12-22.22; very high risk: OR, 8.13; 95% CI, 1.74-37.91); ICU death (moderate risk: OR, 3.65; 95% CI, 1.39-9.56; high risk: OR, 7.97; 95% CI, 3.05-20.82; very high risk: OR, 16.39; 95% CI, 5.99-44.87); and hospital death (moderate risk: OR, 4.19; 95% CI, 1.60-10.94; high risk: OR, 9.75; 95% CI, 3.74-25.45; very high risk: OR, 18.65; 95% CI, 6.81-51.11). Although not increasing in a progressive manner, the ORs for the high-risk groups were significantly associated with a diagnosis of new-onset sepsis (moderate risk: OR, 3.55; 95% CI, 1.10-11.53; high-risk: OR, 4.17; 95% CI, 1.24-14.05; very high risk: OR, 3.98; 95% CI, 0.98-16.18) and with a diagnosis of new-onset hypovolemic shock (moderate risk: OR, 3.22; 95% CI, 0.87-11.85; high risk: OR, 8.42; 95% CI, 2.26-31.41; very high risk: OR, 6.06; 95% CI, 1.47-25.00) (Figure 2).

Stable Cohort Outcomes

Although not statistically significant, the incidence of new-onset AKI and sepsis, and need for new dialysis progressively increased as the risk for hypotension increased. However, new-onset hypovolemic shock, ICU death, and hospital death progressively and significantly increased as the risk for hypotension increased. Ventilator-free days and ICU-free days also decreased progressively with increasing risk for hypotension, but the differences were not significant (Table 6).

Table 6.

Outcomes Overall and According to (s)HYPS Risk Categorization for Stable Cohort.

			(s)HYPS risk category (N = 598^*)
	Overall		Low ≤1.0		Moderate 1.5 to 11.5		High ≥12.0
	(N = 729^*)		(N = 68)		(N = 473)		(N = 57)
Characteristic	N	# (%)	N^†	# (%)	N^†	# (%)	N^†	# (%)	P^‡
Tracheostomy	717	130 (18)	68	16 (24)	471	89 (19)	57	8 (14)	0.402
New-onset Acute Kidney Injury	485	79 (16)	56	7 (13)	305	48 (16)	28	7 (25)	0.330
New-onset Dialysis	690	40 (6)	66	4 (6)	443	20 (5)	53	4 (8)	0.576
New-onset Sepsis	457	80 (18)	49	5 (10)	291	52 (18)	29	6 (21)	0.362
New-onset Hypovolemic Shock	666	67 (10)	65	3 (5)	437	43 (10)	47	12 (26)	0.001
ICU death	729	144 (20)	68	5 (7)	473	95 (20)	57	20 (35)	<0.001
Hospital Death	729	165 (23)	68	5 (7)	473	111 (23)	57	25 (44)	<0.001
28-day outcomes
Ventilator-free days	717	22 (8, 26)	68	23 (16, 25)	471	22 (6, 26)	57	20 (0, 24)	0.104
ICU-free days	725	18 (0, 23)	68	20 (7, 24)	471	18 (0, 23)	57	16 (0, 24)	0.207

Of the 729 stable patients, there were 131who had missing data for HYSP risk because an APACHE-II score was not available.

^†

^‡

(s)HYPS: stable hypotension prediction score; ICU: intensive care unit.

With the use of multiple imputation for missing variables, logistic regression analysis indicated increasing ORs for new-onset AKI (moderate risk: OR, 1.39; 95% CI, 0.61-3.19; high risk: OR, 2.37; 95% CI, 0.78-7.18); new dialysis need (moderate risk: OR, 1.11; 95% CI, 0.38-3.24; high risk: OR, 1.58; 95% CI, 0.38-6.59); new-onset sepsis (moderate risk: OR, 1.99; 95% CI, 0.75-5.25; high risk: OR, 2.07; 95% CI, 0.58-7.38); new-onset hypovolemic shock (moderate risk: OR, 2.24; 95% CI, 0.69-7.30; high risk: OR, 7.41; 95% CI, 2.06-26.62); ICU death (moderate risk: OR, 2.56; 95% CI, 1.04-6.31; high risk: OR, 5.08; 95% CI, 1.87-13.85); and hospital death (moderate risk: OR, 3.03; 95% CI, 1.23-7.42; high risk: OR, 7.08; 95% CI, 2.63-19.07). Only new-onset hypovolemic shock, ICU death, and hospital death had results that were statistically significant (Figure 3).

Discussion

Our study evaluated a prediction score for peri-intubation hypotension and its association with several patient-centered outcomes and clinical conditions. Our results indicate that the HYPS prediction tool is associated with an increased and significant risk for new-onset AKI, need for new dialysis, ventilator- and ICU-free days, and ICU and hospital mortality in a progressive manner as the risk for peri-intubation hypotension increases. We also noted that the high-risk groups, according to the HYPS tool, were associated with clinical conditions of new-onset sepsis and hypovolemic shock, which may explain the propensity for the development of peri-intubation hypotension. In a sensitivity analysis limited to patients who did not have preintubation hemodynamic perturbations (ie, the stable cohort), an increasing prediction score was associated with ICU and hospital mortality and the clinical condition of new-onset hypovolemic shock, adding to the robustness of the study findings.

Our findings are in accord with others in the medical literature that have reported a significantly higher rate of adverse outcomes among patients with hypotension. For example, a systematic review of the effects of intraoperative hypotension on postoperative outcomes showed that organ injury such as AKI, myocardial injury, and stroke may occur with MAP less than 80 mm Hg with a duration of at least 10 minutes.¹⁵ Moreover, in a study of intraoperative hypotension during noncardiac surgery, intraoperative hypotension was common, occurring in 39.5% of patients who had MAP of 75 mm Hg or less, in 19.3% of patients who had MAP of 65 mm Hg or less, and in 7.5% of patients who had MAP of 55 mm Hg or less, and major adverse cardiac and cerebrovascular events in the 30 days after surgery were significantly increased at all MAP thresholds evaluated (12% for MAP ≤75 mm Hg, 17% for MAP ≤65 mm Hg, and 26% for MAP ≤55 mm Hg).¹⁶

In addition to intraoperative hypotension being associated with adverse clinical outcomes, hypotension occurring in hospital units or in the ICU (regardless of the patient's surgery status) portends a poor outcome.^{8,11,12,17–19} Moreover, in an observational study evaluating ICU intubation practices from 29 countries, peri-intubation hemodynamic instability was observed frequently (42%) and was associated with higher ICU mortality (32%).²⁰ Thus, it is now accepted that any hypotension that occurs in the hospital with or without ETI is generally associated with negative outcomes; therefore, timely recognition and treatment of this modifiable risk factor is imperative. Although there is evidence of the negative consequences of hypotension occurring in the hospital, to our knowledge no published studies have assessed an association between a hypotension predictive tool and adverse clinical outcomes or clinical conditions.

Previously we showed that both of our tools reasonably predicted hypotension with an area under the curve of 0.75 for HYPS and 0.71 for (s)HYPS.⁵ Not surprisingly, our scores included several variables known to be associated with poor clinical outcomes (APACHE II, age, sepsis, MAP <65 mm Hg, diuretic use, systolic blood pressure <130 mm Hg, and acute respiratory failure). For example, higher scores for illness severity have been found to be associated with increased mortality.^21,22 Moreover, advanced age has been associated with in-hospital mortality and with mortality after hospital discharge.^20,23,24 Older age is also associated with higher rates of AKI and the need for kidney replacement therapy, most likely because of several factors, including more numerous comorbid conditions, polypharmacy, and derangements in the vascular endothelium. In addition, sepsis is more common among elderly patients than among younger patients, and sepsis-associated AKI is common and occurs in about 1 in 3 patients who have a diagnosis of sepsis.^25,26

The HYPS tools also included hypotension threshold variables such as MAP less than 65 mm Hg and systolic blood pressure less than 130 mm Hg.⁵ As stated previously, hypotension in the ICU is associated with poor outcomes. Our previous work showed that for ICU patients with an MAP of 75 mm Hg or less, outcome rates were higher for major adverse cardiac and cerebrovascular events, 30- and 90-day mortality, AKI and dialysis, and 30-day readmissions than they were for patients with an MAP that was never below that threshold of 75 mm Hg.¹² Moreover, others have noted that ICU patients with an MAP less than 85 mm Hg have adverse outcomes.⁸ This finding is in accord with our finding of increased risk for patients with hypotension (systolic blood pressure <130 mm Hg; MAP would be approximately 85 mm Hg if systolic blood pressure were 130 mm Hg and diastolic blood pressure were 60 mm Hg).

We also noted a higher incidence of new-onset hypovolemic shock with increasing HYPS and (s)HYPS. This is not surprising because a variable in our prediction tools included diuretic use. Volume depletion, a hallmark of hypovolemic shock, could easily become apparent during the transition from negative pressure to positive pressure with ETI.²⁷ The administration of medications known to induce volume depletion (eg, diuretics) before this transition could theoretically worsen the transition. Evidence also suggests that diuretics, which are commonly used in the ICU, have antihypertensive effects in addition to their volume depletion effects.^28,29

We found that higher HYPSs but not higher (s)HYPSs were associated with prolonged mechanical ventilation. Our prediction tool accounts for advanced age and illness severity, both of which have been associated with prolonged mechanical ventilation in the ICU.³⁰ A separate study also noted that postintubation hypotension was associated with a composite end point of overall mortality, ICU length of stay longer than 14 days, duration of mechanical ventilation longer than 7 days, and requirement for kidney replacement therapy.⁶ Others have noted the association between hypotension and increased ICU or hospital length of stay.^31–34 Thus, it is not surprising that as the HYPS prediction risk increases, the association with prolonged mechanical ventilation and length of stay also becomes more evident.

The present study has several strengths. Our analysis included critically ill patients from various geographic areas, so the applicability of our current findings is increased. Moreover, our previously validated HYPS tools reasonably predicted hypotension related to ETI, which further adds to the mounting evidence that even brief episodes of hypotension in critically ill patients are associated with negative consequences. Second, the hemodynamic data analyzed in this study were collected prospectively and in real time. Finally, we demonstrate associations with new-onset organ failure (ie, AKI) and clinical syndromes of sepsis and hypovolemic shock with a hypotension prediction tool. This is substantial as it allows the treating team to be cognizant of the association between peri-intubation hypotension and impeding shock and if risk for peri-intubation hypotension is high, then perhaps changes in the treatment plan may be warranted. In addition, the hypotension prediction tool also signifies to the treatment team that if someone is high risk for hypotension, there odds of developing new-onset organ failure, or ultimately death, are increased and preventive measures should be taken such as pre-intubation treatment with vasopressors or a pre-intubation fluid bolus given associations with sepsis and hypovolemic shock.

Limitations

Our study has several limitations. First, although the hemodynamic data were validated in real time, the granularity was less than ideal and may have led to systemic biases. Ultimately, continuous recordings from an arterial line would have been closer to ideal. Second, this was an observational study, so it had all the biases that are associated with observational study designs and are inherent in post hoc analyses. Third, we reported on associations and not causation. Fourth, there are likely additional variables that we did not assess that could be associated with the outcomes/conditions studied. Fifth, the HYPS tools may have been better analyzed as continuous variables. When analyzing the HYPS tools as a predictor of other outcomes, we treated the score as a categorical variable because the HYPS tools were created primarily to stratify patients by their risk for peri-intubation hypotension. In the present study, we showed that the risk groups that are created with the HYPS tools are also predictive of other outcomes. Moreover, the cutoffs are different for the 2 cohorts because the HYPS tool was used with the full cohort and the (s)HYPS tool was used with the stable cohort. Sixth, we assessed the association of HYPS with multiple outcomes which increases the likelihood of type I error. However, for most outcomes, the unadjusted p-values were <0.001 which would meet criteria for statistical significance after adjustment for multiple comparisons, and in all cases the direction of the findings were consistent with higher HYPS risk categories found to be at increased risk for worse outcomes. Finally, given the exploratory nature of the current investigation, significant associations identified in this study may have been due to chance.

Conclusions

We showed that, according to the validated HYPS and (s)HYPS tools, as the risk of hypotension related to ETI in the ICU increases, the risk of adverse patient outcomes also increases. Our findings provide additional evidence that hypotension in critically ill patients is associated with adverse clinical events and that this hypotension, especially related to ETI, may be associated with clinical syndromes such as impending shock. These risk prediction tools may be used by critical care providers to proactively intervene and correct peri-intubation hypotension, especially given that critically ill patients who have a higher tendency for peri-intubation hypotension may have worse outcomes or may be at increased risk for certain clinical conditions.

Supplemental Material

sj-docx-1-jic-10.1177_08850666221085256 - Supplemental material for Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study*

Supplemental material, sj-docx-1-jic-10.1177_08850666221085256 for Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study* by Nathan J. Smischney, Salim R. Surani, Ashley Montgomery, Pablo Moreno Franco, Cynthia Callahan, Gozde Demiralp, Rudy Tedja, Sarah Lee, Santhi I. Kumar and Ashish K. Khanna in Journal of Intensive Care Medicine

Supplemental Material

sj-docx-2-jic-10.1177_08850666221085256 - Supplemental material for Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study*

Supplemental material, sj-docx-2-jic-10.1177_08850666221085256 for Hypotension Prediction Score for Endotracheal Intubation in Critically Ill Patients: A Post Hoc Analysis of the HEMAIR Study* by Nathan J. Smischney, Salim R. Surani, Ashley Montgomery, Pablo Moreno Franco, Cynthia Callahan, Gozde Demiralp, Rudy Tedja, Sarah Lee, Santhi I. Kumar and Ashish K. Khanna in Journal of Intensive Care Medicine

Footnotes

Acknowledgments

The authors would like to acknowledge the following collaborators for the contribution of data toward the current manuscript: Rahul Kashyap, MBBS, MBA; Ernesto Brauer, MD; Lee E. Morrow, MD, MSc; Mohamed O. Seisa, MD; Darrell R. Schroeder, MS; Daniel A. Diedrich, MD; Uchenna R. Ofoma, MD, MS; David A. Kaufman, MD; Ayan Sen, MD; Chakradhar Venkata, MD; Peter Morris, MD; Vikas Bansal, MBBS, MPH; and Mariya Geube, MD. Randall J. Fritz, DVM, Mayo Clinic, substantively edited the manuscript. The Scientific Publications staff at Mayo Clinic provided proofreading, administrative, and clerical support.

Author Contributions

All authors contributed equally in the preparation of the current manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval

Not applicable, because this article does not contain any studies with human or animal subjects.

ORCID iDs

Nathan J. Smischney

Santhi I. Kumar

Supplemental Material

Supplemental material for this article is available online.

Abbreviations

Appendixes

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