Early Respiratory Outcomes Following Cardiac Surgery in Patients
with COVID-19
Running title : Respiratory Outcomes PostCardiac Surgery
COVID-19
Authors :
Khosro Barkhordari1*, Mohamad Reza
Khajavi2, Sepideh Nikkhah3,Mahmood Shirzad4, Jamshid
Bagheri4, Sepehr Barkhordari5,
Katayun Kharazmian3, Marjan Nosrati6
1- Department of Anesthesiology and Critical Care, Tehran Heart Center,
Tehran University of Medical Sciences, Tehran, Iran
2- Department of Anesthesiology and Critical Care, Sina Hospital, Tehran
University of Medical Sciences, Tehran, Iran
4-Department of cardiac surgery, Tehran Heart Center, Tehran University
of Medical Sciences, Tehran, Iran
3- Food and Drug Bureau, Ministry of Health and Medical Education,
Tehran, Iran
5- College of Biological Sciences, University of California, Davis, USA
6- Department of disease control, Tehran heart center, Tehran, Iran
*Correspondence: kh.barkhordari@gmail.com. Department of anesthesiology
and critical care, Tehran heart Center, Tehran University of Medical
Sciences, Tehran, IRAN, 1411713138
Tel: +989123903641
Key words : cardiac surgery, respiratory, outcome, COVID-19
Abstract
The objective of this study was to describe early respiratory outcomes
of asymptomatic COVID-19 patients after cardiac surgery.
In this retrospective clinical study (case series) we reviewed and
analyzed patient clinical data of 25 covid-19 asymptomatic patients that
underwent urgent or emergent cardiac surgery between February 29 and
April 10, 2020 in Tehran Heart Center Hospital.
Median of age was 63 years (IQR, 52-67), Euro SCORE 7.50 (IQR, 6.5-8.5)
and body mass index 26.3 (IQR, 22.5-28.6). 68% of patients had one or
more comorbidities. Hypertension (56%) was the most common followed by
Diabetes type 2 (40%). Off-pump cardiac surgery was done in 4 patients
and on-pump on 21 patients with median CPB time of 85 minutes (IQR,
50-147.50). Median anesthesia time was 4.5 hours (IQR, 4-5). Median
oxygen index and Fio2 on ventilator were 10 cmH20 (IQR, 9.5-10.5) and
0.64(IQR, 0.60-0.64) respectively. Median pao2/Fio2 was 231(IQR,
184-261). There was one case of extubation failure. The Median
intubation time and length of ICU stay were 13 hours (IQR, 9.5-18) and 3
days (IQR, 2-4) respectively. Overall mortality was 16%. Readmission
rate to ICU was 16% with. In this group respiratory outcome was worse
with median Pao2/Fio2 84.5 (75-122), oxygen index of 4.38(IQR, 3.77-5.1)
and morality rate of 75%.
Conclusion: Based on the results of this study, very early post-cardiac
surgery respiratory outcomes in asymptomatic COVID-19 patients are
apparently smooth; nonetheless, readmission to the ICU is high. Overall
respiratory outcomes are poor especially for those who readmitted to
ICU.
Introduction
Corona virus disease 2019 (COVID -19) has been announced as a pandemic
on March 11, by World Health Organization (WHO). Unfortunately, IRAN is
one of the hotspot countries among many other countries. Our hospital,
Tehran Heart Center, was one of few referral hospitals dedicated to
emergency heart surgery patients by Ministry of Health. The lung is the
main organ that is affected by this disease. About 80% of symptomatic
COVID-19 patients develop mild disease, and 15% develop severe disease
(with hypoxemia, dyspnea and tachypnea), while 5% become critically ill
with respiratory failure, septic shock and/or multi-organ
dysfunction1. Abnormalities are visible on chest CT
cans in 85% of patients2. A majority of patients with
severe respiratory disease need invasive mechanical
ventilation3. Inflammatory renal and lung diseases and
at extreme acute respiratory distress syndrome (ARDS) and acute renal
failure are serious complications of both COVID-19 and cardiopulmonary
by-pass (CPB) 3,4. There are few studies about
clinical outcomes of covid-19 patients in intensive care unit. ICU
mortality is 22-66% in nonsurgical patients3,5. In a
recent large case series in Italy the mortality rate of patients
admitted to ICU was about 26 percent3. A lot of
patients had ARDS and needed high fraction of inspiratory oxygen (Fio2)
and positive end expiratory pressure (PEEP). There is a very little
information about clinical outcomes of surgical COVID-19 patients.
Surgery itself and mechanical ventilation have own impacts on the lung.
CPB aggravates these injuries even further in cardiac surgery
patients6. In a retrospective cohort study of general
surgical covid-19 patients, all had lung CT abnormalities after surgery
and mortality rate in ICU was 20.5%7. Studies about
airway management during surgery in patients with COVID- 19 are rare and
we worked based on recommendations and suggestions of
experties.8 Since at the time of writing of this
article, we couldn’t find any study regarding post anesthesia
respiratory outcomes of cardiac surgery patients. The aim of our study
was to analyze the early post-anesthesia respiratory outcomes of
asymptomatic COVID-19 cardiac surgery patients who underwent urgent or
emergent surgery on discern of cardiac surgeon and cardiologist. Experts
recommend lung protection strategy for intubated COVID-19 patients, like
other ARDS patients9,10. We worked based on that
recommendations. Since at the time of writing this article there was not
any study in cardiac surgery patients. We think our small data can
provide knowledge about post-operation respiratory course in cardiac
surgery patients.
2. Materials and Methods:
Patients:
In this retrospective study data of patients with COVID-19 who underwent
urgent or emergent cardiac surgery in Tehran Heart Center Hospital
between February 29 and April 10, 2020 and fulfilled our study criteria
were reviewed and analyzed. Informed consent obtained from all patients
regarding using their medical information for research purposes .This
study was approved by research committee of Tehran heart center for
medical record review. The diagnosis of COVID-18 was the responsibility
of a team comprising a radiologist, and infectious disease specialist,
and Intensivist based on positive reverse transcription-polymerase chain
reaction(RT-PCR) tests or chest CT according to the WHO interim
guidance10. Patients were asymptomatic at admission
time. All of the patients were receiving hydroxychloroquine and
azithromycin and some of them antiviral drugs. General anesthesia
induced with routine anesthetic drugs by in-charged anesthesiologists.
Majority of patients received Midazolam, Fentanyl, Propofol, and
Atracurium as induction drugs. For maintenance propofol and fentanyl
infusions and divided doses of Atracurium and Panccuronium were used as
needed. Eight of the patients received Isoflurane, in addition to above
drugs, both during induction and maintenance of anesthesia. On-pump
cardiac surgery was done in 21 patients and 4 had off-pump surgery. In
open heart ICU, patients were put on routine post cardiac surgery care
and monitoring. Ventilator parameters were adjusted by anesthesiologists
and intensivists in charge of patients based on hemodynamic, respiratory
and ABG indices. Based on hemodynamic and respiratory indices low tidal
volumes (6-8 ml/kg IBW) and different amounts of PEEP were used. Depend
on clinical conditions of patients, our ICU early extubation protocol
strategy followed as could as possible. Fluid management was based on
hemodynamic monitoring indices, urine output, and clinical judgments and
also conservative volume strategy was applied as could as possible.
Data collection:
The patient characteristics and data collected from medical records and
ICU flow sheets. Data of patients with age≤ 18, active respiratory
disease, patients with renal and hepatic failure, history of
uncontrolled respiratory diseases excluded from reviewing. Data in ICU
included hemodynamic parameters, Mean Airway Pressure (MAWP), amount of
PEEP, Fio2, Pao2, Paco2 ,fluid balance in three day, serum creatinine,
post-operative bleeding, reopening of chest due to surgical
complications, amount of received PRBC and blood components among
others. Euro SCORE II was used for risk
stratification11.
Outcomes:
Our early respiratory outcomes were extubation failure rate, intubation
time, Pao2/Fio2 ratio, Oxygen index, and Mean Airway Pressure (MAWP).
Other outcomes were: length of stay in ICU (ICULOS), readmission to ICU,
AKI, and mortality in 30 days after surgery. Pao2/Fio2 ratio and
Oxygenation index calculated from computation of pao2, Fio2, MAWP
variables based on their specific formula. Based on Berlin definition,
severity of ARDS in patients was determined using Pao2/Fio2
ratios12. AKI of patients defined based on changes on
creatinine according to KDIGO guidelines for postoperative
patients13.
Statistical analysis:
Continuous variables are presented as mean and median. Categorical
variables were expressed as frequencies and percentages. Statistical
analysis was performed by SPSS software version 21.
3. Results:
A total 25 patients who had COVID-19 and underwent cardiac surgery were
enrolled in the study. 21 patients had positive test and 4 had positive
chest HRCT. Basic characteristics of patients are shown in Table 1.
Seventy two percent of patients were male. The median of age was 63
years (IQR, 52-67). Median EuroSCORE and body mass index were 7.50 (IQR,
6.5-8.5), 26.3 (IQR, 22.5-28.6), respectively. 68% of patients had one
or more comorbidities. Hypertension (56%) was the most common followed
by Diabetes type 2 (40%). 20% of patients were Cigarette smokers. Mean
left ventricular ejection fraction (LVEF) was 43.53 %( SD±8.40). Four
patients (16%) had history of respiratory diseases, one of them asthma
and three COPD, but their diseases were under controlled. Off-pump
cardiac surgery was done in 4 of our patients and 21(84%) patients
underwent on-pump with median CPB time of 85 minutes (IQR, 50-147). The
types of surgery were diverse that is shown in Table 2. Median
anesthesia time was 4.5 hours (IQR, 4.5-5). 14 patients received
inotropes during surgery with maximum doses of norepinephrine
0.08µ/kg/min, dobutamine10 µ/kg/min and epinephrine 0.05 µg/kg/min. One
patient needed IABP. Mean Pao2, Fio2, Pao2/Fio2 ratio, MAWP and Oxygen
index during first 6 hours after surgery were 146 (SD± 27.99) mmHg,
0.63(SD± 0.48), 232.82 (SD± 49.23), 10 cmH20 (SD± 1.20) and 4.47(SD±
1.13), respectively. Median PEEP was 5.5(5.25-6). Base on Berlin
definition of ARDS, at entering to ICU one patients had severe ARDS,
12(44.4%) moderate and 10(37%) mild ARDS but after 8 hours there was
no severe ARDS, 6 (24%) had moderate and 17(48%) mild ARDS. 40% of
patients had AKI in post-operative day 3. 3(12%) patients had
reoperation due to bleeding. PRBC transfusion done in 14(56%) of
patients. Mean hemodynamic parameters until extubation are showed on
Table 1. Majority of patients had normal sinus rhythm (84%), 18% sinus
tachycardia, 12% atrial fibrillation and 1 persistent ventricular
tachycardia that needs DC Shock. One of patients re-intubated after 8
hours of extubation. Median intubation time was 13hours (IQR, 18-9.5)
and median first ICU LOS was 3 days (2-4). These figures are not include
the patients readmitted to the ICU. Four patients (16%) readmitted to
ICU with median time from discharge to readmission to ICU of 4.5 days
(IQR, 3-6.5). In the readmitted patients the Fio2 and Oxygen index, and
PEEP were higher, and Pao2/Fio2 ratio was lower than main group.
Table3.Three (75%) of these 4 patients died.
4. Conclusions:
To the best of our knowledge, at the time of the writing of the present
study, the literature contains no investigation on the respiratory
outcomes of post-cardiac surgery patients with COVID-19. In this case
series, we retrospectively reviewed basic characteristics and clinical
data of 25 patients that underwent emergent or urgent cardiac surgeries
at the discretion of cardiac surgeons and cardiologists. As our country
is one of the several global hot spots of COVID-19, all our cardiac
surgery patients routinely preoperative COVID-19 test and computed
tomography(CT).The diagnosis of COVID-18 was the responsibility of a
team comprising a radiologist, and infectious disease specialist, and
intensivist based on positive reverse transcription-polymerase chain
reaction(RT-PCR) tests or chest CT according to the WHO interim
guidance10. Twenty-one patients tested positive for
COVID-19, and 4 were diagnosed based on their chest CT and history of
close contact with COVID-19 patients. A recent retrospective study in
China described clinical outcomes of general surgical patients with
diverse types of surgeries7. In comparison with the
patients in that study our patients were older. (mean age, 63 years).
The median EuroSCORE of our patients was 7.50 (IQR, 6.5-8.5) indicating
higher risk of morbidity and mortality. 68% of our patients had at
least one medical condition this is more than the surgical patients that
needed ICU admission in the Chinese study. With respect to medical
conditions, our patients were similar to the nonsurgical patients
admitted to the ICU in a study by Grasseli et al.3,7Chiming in with other studies, hypertension was the most common
comorbidity in our investigation. Hemodynamic complications and both
cardiogenic and septic shocks are not uncommon in
COVID-197,14.But our patients had relatively
acceptable hemodynamic parameters after surgery.Fourteen (64%) patients
received usual doses and four (16%) needed high doses of inotropes in
current study. In a study by lei et al. on non-cardiac surgery patients,
53% of the patients admitted to the ICU had shock and 33% had cardiac
arrhythmias. Because inotropes are frequently used to support
hemodynamics in cardiac surgery patients, we cannot compare the
incidence rate of shock between that study and ours; nonetheless,
overall, our patients were hemodynamically stable after surgery. One of
our valve surgery patients needed IABP in operating room. Another
patient that underwent on-pump CABG needed DC shock twice, which was
because of sustained episodes of ventricular fibrillation. This patient
had no history of any medical conditions and subsequently had a
straightforward postoperative ICU course. In a retrospective study that
compared postoperative outcomes between patients undergoing emergency
CABG and those undergoing elective CABG, morbidity and mortality were
higher in former group15. In that study the mean CPB
time was 80.2 ± 39.7 minutes, which is shorter than our CPB time (99.75
±63.5). Nevertheless, given the diversity in our surgical operations,
this CPB time is expectable. In our study rate of acute kidney injury
(AKI) on the third postoperative day was 40% which is higher than the
rate in COVID-19 ICU patients following general surgery and non COVID
emergency cardiac surgery patients.7,15 Although some
anesthetic agents may poses anti-inflammatory effects, surgery itself,
specially cardiac surgery, and CPB cause inflammatory response and acute
lung injury 16,17. Upon admission to ICU, based on the
Berlin ARDS definition, only one of our patients had severe ARDS, while
the majority of patients had moderate (44.4%), or mild ARDS (37%). The
mean airway pressure (9.96 SD±1.48) was not unexpectedly high,
indicating that fluid overload and heart stunning might also have a role
in hypoxemia. Moreover, lesser severity of ARDS may be explained by the
fact that our patients were asymptomatic and anesthetics and muscular
relaxants affect the compliance and resistance of the lung. The median
airway pressure and Fio2 of intubated patients were 10 cmH20 (IQR,
9.50-10.50), and 0.64 (IQR, 0.60-0.64) respectively, which are lower
than the values reported in the study by Grasselli et
al3. In addition the median of Pao2/Fio2 was 231(IQR,
184-261), which was higher than nonsurgical intubated patients. Our
patients were asymptomatic, whereas the ICU patients in the study by
Grasselli and colleages srffered from severe pneumonia. We used the
amount of PEEP based on hemodynamic and respiratory parameters. Because
at least for the first hours of postoperative period, the majority of
cardiac surgery patients have hemodynamic instability, the median PEEP
in our patients [6 IQR, (5-6)] was lower than in nonsurgical
ventilated patients. Oxygenation was acceptable with this amount of PEEP
and Fio2, and the median oxygen index was [4.3 (IQR, 3.8-5.2)] and
relatively constant over time. Emergent or urgency surgery, old age,
comorbidities, and high frailty scores are associated with longer
mechanical ventilation in cardiac surgery patients18.
Our mean intubation time was 22.25 hours and all the patients extubated
within 99 hours post procedurally, and 44% of them were extubated
within twelve hours after admission to the ICU. It is worth noting that
this figure does not include the patients that readmitted to the the
ICU. We had one case of extubation failure, this patient was
re-intubated because of hypoxemia and respiratory failure 8 hours later.
He was again extubated after 24 hours and discharged from the ICU;
however, 2 days later, he was readmitted to ICU with severe respiratory
insufficiency, septic shock, ventricular arrhythmia and unfortunately
expired 5 days afterward. One of our patients died in the first 7 days
of ICU stay. This patient had fever, arrhythmias from sinus tachycardia
to sustained ventricular fibrillation and agitation died at
7th day. He was never weaned from ventilator, with
severe ARDS, metabolic acidosis, bradycardia and asystole representing
the clinical pictures of his death. Unlike the post- surgery patients in
the study by Lei et al, in which fever was most common symptom, a low
spo2 (<87%) was the most common first sign in post-ICU and
wards (80%). Fever (72%), respiratory distress (64%), headache
(28%), and cough (28%) constituted the common signs and symptoms.
Majority of patients improved with routine supportive cares. Four
patients were readmitted after discharge from the ICU due to respiratory
and hemodynamic problems.
Respiratory and ventilator indices during this second stay in the ICU
were unfavorable. (Table 3). Based on the Berlin definition, 3 (75%) of
patients suffered from severe ARDS and 1 had moderate ARDS. Median PEEP
and Fio2 was much higher than main group. In this group Lymphocyte count
was lower and C-reactive protein (CRP) was higher than in the main group
of patients. CRP in cardiac surgery patients is already high due to
inflammation; still, in our re-admitted group, the CRP level was much
higher than in the main group. Three (75%) of these patients died,
which by comparison with the nonsurgical ICU patients in the study by
Grasselli et al is high. Acute viral myocarditis was the first
differential diagnosis of 2 of these patients as decided by the
cardiologist in charge. These patients had severe tachycardia, low EF,
and high values of troponin enzymes (Table 3). This indicates that
symptomatic post-cardiac surgery patients carry a very high risk of
mortality, although the early postoperative respiratory and hemodynamic
outcomes of our patients appeared acceptable with only 1 case of
extubation failure and mortality in the first week of post-operative
period. High rate of ICU readmission (16%) and the very high mortality
rate (75%) among this group were alarming, however.
In light of the results of the present study, it can be concluded that
the very early postoperative respiratory outcomes in asymptomatic
COVID-19 emergent and urgent cardiac surgery patients are smooth;
nonetheless, readmission to the ICU is high. Thus in this group of
patients we should expect very high rates of severe ARDS and mortality.
We suggest that cardiac surgical operations be postponed unless they are
emergent.
This study has several limitations. First, this study is a retrospective
study and data collected from medical records and flow sheets so some
data are missed. Secondly, the sample size is too small to compare
between groups. Third, patients in post ICU and other wards were not
monitored same as open heart ICU.