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Brief Report

Fewer Intubations but Higher Mortality Among Intubated Coronavirus Disease 2019 Patients During the Second Than the First Wave

Routsi, Christina MD, PhD; Kokkoris, Stelios MD, PhD; Siempos, Ilias MD, PhD; Magira, Eleni MD, PhD; Kotanidou, Anastasia MD, PhD; Zakynthinos, Spyros MD, PhD

Author Information
doi: 10.1097/CCE.0000000000000531
  • Open
  • COVID-19

Abstract

The rate of intubation and hospital mortality of intubated patients with coronavirus disease 2019 (COVID-19) in our ICUs at “Evangelismos” Hospital, Athens, Greece, during the first wave of the pandemic was reported to be 82% and 39%, respectively (1). Since then, changes in pharmacological treatments for severely ill patients with COVID-19 have been incorporated into clinical practice, both by their use (corticosteroids [2] and remdesivir [3]) and by stopping them (e.g., hydroxychloroquine). Hence, it would be expected that this pharmacological adaptation, combined with gained experience and improved algorithms of using oxygen treatment, would have a significant impact on the rate of intubation and mortality of intubated ICU patients. We, therefore, sought to compare the above outcomes in our ICUs between the first and second waves of the pandemic. The study was approved by the hospital institutional review boards (ethical committee of “Evangelismos” Hospital; 116/31 March 2021).

Comparison between the first and second waves regarding various patient data on ICU admission, interventions in the ICU, and outcomes is detailed in Tables 1 and 2. The percentage of intubated ICU patients (i.e., patients who were already intubated on ICU admission or intubated after admission) dropped from 82% during the first wave (from March to July 2020) to 66% during the second wave (from September 2020 to January 2021) (p = 0.042). However, the absolute number of intubated ICU patients was more than three times lower during the first compared with the second wave (41 vs 140 patients), compatible with a much stronger second wave in Greece in terms of the number of cases and deaths (4).

TABLE 1. - Demographics and Clinical and Laboratory Data on ICU Admission of Patients With Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia During the First and the Second Severe Acute Respiratory Syndrome Coronavirus-2 Wave
Variable All (n = 262)a First Wave (n = 50) Second Wave (n = 212)a pb
Age, yr, median (IQR) 67 (57–76) 64 (58–72) 68 (56–77) 0.291
 ≤ 64 119 (45.4) 26 (52.0) 93 (43.9) 0.378
 ≥ 65 143 (54.6) 24 (48.0) 119 (56.1)
Age in intubated, yr, median (IQR) 70 (59–80)c 66 (59–73)d 70 (59–82)e 0.074
 ≤ 64 72 (39.8) 19 (46.3) 53 (37.9) 0.427
 ≥ 65 109 (60.2) 22 (53.7) 87 (62.1)
Gender, male 186 (71.0) 38 (76.0) 148 (70.0) 0.487
Comorbidity
 Hypertension 103 (39.3) 14 (28.0) 89 (42.0) 0.096
 Diabetes mellitus 70 (26.7) 9 (18.0) 61 (28.8) 0.170
 Cardiovascularf 67 (25.6) 6 (12.0) 61 (28.8) 0.023
 Malignancyg 19 (7.3) 5 (10.0) 14 (6.6) 0.596
 Obesityh 32 (12.2) 5 (10.0) 27 (12.7) 0.770
 Chronic lung disease 31 (11.8) 4 (8.0) 27 (12.7) 0.490
 Chronic renal failure 17 (6.5) 1 (2.0) 16 (7.5) 0.265
 Comorbidities (≥ 2) 134 (51.1) 18 (36.0) 116 (54.7) 0.026
APACHE II score, median (IQR) 13 (9–19) 12 (8–17) 13 (9–20) 0.140
APACHE II score in intubated, median (IQR) 15 (11–22)c 14 (9–18)d 17 (12–23)e 0.029
Sequential Organ Failure Assessment score, median (IQR) 6 (2–9) 7 (3–9) 6 (2–9) 0.057
Laboratory data, median (IQR)
 C-reactive protein, mg/dLi 12.4 (5.4–19.6) 14.2 (7.7–24.6) 11.2 (4.6–18.9) 0.041
 Procalcitonin, ng/mLj 0.26 (0.11–1.07) 0.43 (0.12–0.94) 0.25 (0.11–1.36) 0.840
d-dimer, μg/mLk 1.30 (0.67–2.49) 1.23 (0.52–2.46) 1.30 (0.69–2.56) 0.529
 Troponin Τ, pg/mLl 17 (8–62) 15 (10–52) 20 (8–79) 0.509
 Lactate, mmol/L 1.6 (1.2–2.1) 1.3 (1.0–1.8) 1.7 (1.3–2.3) 0.001
Arterial blood gases, median (IQR)
 Pao 2, mm Hg 90 (75–118) 100 (85–126) 87 (72–112) 0.034
 Pao 2/Fio 2, mm Hg 123 (89–179) 121 (86–171) 124 (90–180) 0.616
 Paco 2, mm Hg 40 (33–46) 40 (33–45) 40 (33–46) 0.754
 pH 7.39 (7.30–7.45) 7.39 (7.32–7.44) 7.40 (7.30–7.46) 0.506
Respiratory parameters at day of intubation, median (IQR)
 positive end-expiratory pressure, cm H2O 12 (10–15)c 14 (12–16)d 12 (10–15)e 0.016
 Plateau pressure, cm H2O 26 (23–29)c 27 (25–29)d 26 (23–29)e 0.633
 Driving pressure, cm H2O 13 (12–15)c 13 (11–15)d 13 (12–16)e 0.131
 Static compliance, mL/cm H2O 36 (30–41)c 40 (32–50)d 34 (28–40)e 0.037
Usage of vasopressors 85 (32) 33 (66) 52 (25) < 0.001
APACHE = Acute Physiology and Chronic Health Evaluation, IQR = interquartile range.
aThirty-two patients who are still hospitalized in the ICU.
bMann-Whitney U test and χ2 with Yates correction or Fisher exact test comparing the first wave and the second wave.
cA total of 181 patients who received invasive mechanical ventilation.
dForty-one patients who received invasive mechanical ventilation.
eOne hundred forty patients who received invasive mechanical ventilation.
fCoronary artery disease and/or congestive heart failure.
gCurrent malignancy (lymphoma, leukemia, etc, and patients under chemotherapy).
hBody mass index > 30 kg/m2.
iUpper limit of normal 0.5 mg/dL.
jUpper limit of normal 0.1 ng/mL.
kUpper limit of normal 0.3 μg/mL.
lUpper limit of normal 14 pg/mL.
Data are expressed as n (%) unless otherwise indicated.

TABLE 2. - Interventions in the ICU and Outcomes of Patients With Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia During the First and the Second Coronavirus Disease 2019 Wave
Variable All (n = 262)a First Wave (n = 50) Second Wave (n = 212)a pb
High-flow nasal cannula 130 (50) 14 (28) 116 (55) 0.001
Noninvasive mechanical ventilation 6 (2) 2 (4) 4 (2) 0.709
Invasive mechanical ventilation 181 (69) 41 (82) 140 (66) 0.042
 Time to intubation, median (IQR) 2 (0–4)c 2 (0–3)d 2 (0–4)e 0.849
 Neuromuscular blockade 142 (78)c 26 (63)d 116 (83)e 0.850
 Prone position 83 (46)c 6 (15)d 77 (55)e 0.001
Usage of vasopressors 159 (61) 34(68) 125 (59) 0.310
Days on vasopressors, median (IQR) 7 (2–14) 6 (2–13) 7 (2–15) 0.847
Renal replacement therapy 76 (29) 13 (26) 63 (30) 0.728
 Renal replacement therapy days, median (IQR) 14 (10–25) 15(11–24) 13 (9–26) 0.570
Selected inpatient medications
 Hydroxychloroquine 56 (21) 44 (88) 12 (6) < 0.001
 Azithromycin 46 (18) 38 (76) 8 (4) < 0.001
 Lopinavir/ritonavir 18 (7) 18 (36) 0 (0) < 0.001
 Anti-interleukin-6 antibody 5 (2) 5 (10) 0 (0) < 0.001
 Remdesivir 93 (35) 3 (6) 90 (42) < 0.001
 Glucocorticoids 217 (83) 5 (10) 212 (100) < 0.001
Outcomes
 Follow-up, d, median (range) 54 (15–160) 50 (29–88) 62 (15–160) NA
 Successful extubationf 55/181 (30) 17/41 (41) 38/140 (27) 0.020
  Time to successful extubation, d, median (IQR)f 10 (5–15)c 9 (5–14)d 10 (4–16)e 0.813
 Tracheostomy 54 (30)c 12 (29)d 42 (30)e 0.642
  Time to tracheostomy, d, median (IQR) 22 (18–26)c 21 (19–26)d 22 (18–26)e 0.968
 Mechanical ventilation days, median (IQR) 12 (6–22)c 13 (9–33)d 11 (6–20)e 0.080
 ICU days, median (IQR) 13 (7–22) 14 (9–31) 12 (7–22) 0.083
 Hospital days, median (IQR) 19 (8–28) 21 (10–32) 18 (7–27) 0.117
 28-d mortality 84 (32) 12 (24) 72 (34) 0.234
 28-d mortality in intubated 84/181 (46) 12/41 (29) 72/140 (51) 0.020
 ICU mortality 100 (38) 16 (32) 84 (40) 0.403
 ICU mortality in intubated 100/181 (55) 16/41 (39) 84/140 (60) 0.028
 Hospital mortality 100 (38) 16 (32) 84 (40) 0.403
 Hospital mortality in intubated 100/181 (55) 16/41 (39) 84/140 (60) 0.028
 ICU and hospital mortality in nonintubated 0/81 (0) 0/9 (0) 0/72 (0) 1.000
 Still in the ICU 32 (12) 0 (0) 32 (15) NA
 Still intubated in the ICU 14/181 (8) 0/41 (0) 14/140 (10) NA
IQR = interquartile range, NA = not applicable.
aThirty-two patients who are still hospitalized in the ICU.
bMann-Whitney U test and χ2 with Yates correction or Fisher exact test comparing the first wave and the second wave.
cOne hundred eighty-one patients who received invasive mechanical ventilation.
dForty-one patients who received invasive mechanical ventilation.
eOne hundred forty patients who received invasive mechanical ventilation.
fAmong patients who did not have a tracheostomy.
Data are expressed as n (%) unless otherwise indicated.

ICU or hospital mortality of intubated ICU patients increased from 39% during the first wave to 60% during the second wave (p = 0.028). Intubated patients of the second compared with the first wave had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and lactate level and lower positive end-expiratory pressure (PEEP) and respiratory system static compliance, were more likely to suffer from cardiovascular comorbidities, and tended to be older. The binary logistic regression model that was built for hospital mortality as the dependent variable in intubated patients who received invasive mechanical ventilation and covariates all variables that were significantly correlated with hospital mortality as demarcated in the univariate logistic regression testing (i.e., age, APACHE II score, cardiovascular comorbidity [yes vs no], lactate, PEEP, Sequential Organ Failure Assessment score, and wave (first vs second)] distinguished only APACHE II score (odds ratio = 1.40 with 95% CI 1.14—1.72, p = 0.001) as significant predictor of hospital mortality. Neither other comorbidities (i.e., hypertension, diabetes, obesity, and chronic lung disease or renal failure), laboratory and respiratory data (i.e., troponin, d-dimer, C-reactive protein, procalcitonin, Pao2, Pao2/Fio2, and respiratory system static compliance), and interventions (i.e., usage of prone position and neuromuscular blockade), nor pharmacological treatments (i.e., usage of glucocorticoids, remdesivir, or their combination) were significantly correlated with hospital mortality in the univariate logistic regression testing.

Although our study is single-center, this could be considered a strength because similar criteria of ICU admission and tracheal intubation were used allowing for comparison between the two waves. In addition, our center did not experience any difficulties in terms of supplies and materials or a shortage of ICU capacity since all critically ill patients with COVID-19 regardless of their age and comorbidities were admitted to our ICUs in time; indeed, lack of ICU beds did not occur in any of the two waves, at least in the area covered by our hospital, due to the opening of a large number of new ICU beds during the second wave (5). Although the physician or nurse-to-patient ratio did not substantially change between the two waves (5), an overwhelming number of patients signify a noticeable stress on the healthcare system. Indeed, the increase in staff required attending a more than three times higher volume of intubated patients during the second wave was not frequently made by experienced critical care physicians and nurses, and this could have played a role in outcome.

The APACHE II score estimates ICU mortality based on a number of laboratory values and patient signs taking both acute and chronic disease into account. The finding that only APACHE II score was the sole independent predictor of ICU or hospital mortality is intriguing. The abovementioned relative lack of experienced ICU personnel during the second wave could have contributed to increased APACHE II score. Furthermore, due to the more severe second wave, it is probable that more frequently patients with chronic health problems developed the serious form of the disease and increased APACHE II score reflected the overall increase in patients’ comorbidities during the second wave (Table 1). Finally, the same change in the use of drugs and algorithms of oxygen treatment that could cause the reduction of the percentage of intubated ICU patients might be a reason of increased mortality in those patients who were eventually intubated by increasing their APACHE II score.

In conclusion, we found that progress in the understanding of the COVID-19 along with pharmacological adaptations and other measures (6) may have led to fewer intubations over time. However, it may be alarming that the same progress does not seem to be translated into improved outcomes of intubated patients with COVID-19 (7,8). It is possible that the same change in the use of drugs and algorithms of oxygen treatment that could cause fewer intubations of ICU patients might be a reason of increased mortality in those patients who are eventually intubated. Furthermore, the relative staff inexperience and overall increase in patients’ comorbidities during the second wave could have contributed to increased APACHE II score and mortality of intubated patients.

ACKNOWLEDGMENTS

We thank our colleagues in the First Department of Intensive Care Medicine, School of Medicine, National and Kapodistrian University of Athens, at “Evangelismos” Hospital: Charikleia Vrettou, Dimitris Zervakis, Eleni Ischaki, Sotiris Malahias, Ioanna Sigala, Andreas Asimakos, Theodora Daidou, Panagiotis Kaltsas, Evangelia Douka, Adamandia Sotiriou, Vassiliki Markaki, Prodromos Temberikidis, Apostolos Koroneos, Panagiotis Politis, Zafiria Mastora, Efrosini Dima, Theodoros Tsoutsouras, Ioannis Papahatzakis, Panagiota Gioni, Athina Strilakou, Aikaterini Maraguti, Eleftheria Mizi, Ageliki Kanavou, Aikaterini Sarri, Evdokia Gavrielatou, Spyros Mentzelopoulos, and Ioannis Kalomenidis, as well as to all the residents who took care of the patients.

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Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.