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. 2021 Feb 11;16(2):e0246724. doi: 10.1371/journal.pone.0246724

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: A retrospective analysis

Christina M Möller 1, Peter-Paul Ellmauer 1, Florian Zeman 2, Diane Bitzinger 1, Bernhard Flörchinger 3, Bernhard M Graf 1, York A Zausig 1,4,*
Editor: Aleksandar R Zivkovic5
PMCID: PMC7877985  PMID: 33571258

Abstract

Objectives

Surgery for acute type A aortic dissection is associated with several perioperative complications, such as acute respiratory dysfunction (ARD). The aim of this study was to investigate perioperative risk factors involved in the development of ARD and whether antibiotic treatment has an impact.

Methods

243 patients underwent surgery for acute type A aortic dissection between 2008 and 2017. The patients were retrospectively divided into the ARD and NON-ARD group. ARD was defined as PaO2/FiO2 ≤ 200 mmHg (PF ratio) within 48 hours after surgery. All patients received either narrow- or broad-spectrum antibiotics.

Results

After the exclusion of 42 patients, 201 patients were analyzed. The PF ratio of the ARD group was significantly lower than of the NON-ARD group within the first 7 days. ARD patients (n = 111) were significantly older (p = .031) and had a higher body mass index (BMI) (p = .017). ARD patients required longer postoperative ventilation (2493 vs. 4695 [min], p = .006) and spent more days in the intensive care unit (7.0 vs. 8.9 [days], p = .043) compared to NON-ARD. The mortality was significantly lower for ARD than for NON-ARD patients (p = .030). The incidence of pneumonia was independent of the antibiotic treatment regime (p = .391). Renal and neurological complication rate was higher in patients treated with broad-spectrum antibiotic.

Conclusion

ARD is the main complication (55%) that occurs approximately 24 hours after surgery for acute type A aortic dissection. The preoperative risk factors for ARD were higher age and increased BMI. Patients on broad-spectrum antibiotics did not show an improved postoperative outcome compared to patients with narrow-spectrum antibiotics.

Introduction

Acute type A aortic dissection is a life-threatening disease with an incidence of approximately 2–16 cases/100 000 inhabitants in Europe per year and a preoperative mortality of approximately 17.6% [13]. After the patient survived surgery, there is still a high in-hospital mortality of more than 25% [4]. The high mortality rate is caused by various perioperative complications [5, 6].

One of the major and most frequent complications is acute respiratory dysfunction (ARD). Approximately 13% of these patients suffer from ARD, which usually occurs within the first 72 hours after surgery [7]. The consequences of pulmonary dysfunction are a prolonged stay in the intensive care unit (ICU), longer time of mechanical ventilation, higher risk of pneumonia, higher hospital costs and an increased rate of in-hospital mortality [8]. Currently, neither the pathophysiology of ARD nor its risk factors are well understood.

This study aimed to outline perioperative risk factors associated with the development of postoperative ARD in patients suffering from acute type A dissection. Furthermore, we investigated whether the incidence and development of ARD is influenced by the postoperative early use of narrow-spectrum vs. broad-spectrum antibiotics.

Materials and methods

After obtaining approval from the University of Regensburg’s Ethics Commission (No: 16-104-0278), all patients who underwent surgery for acute type A aortic dissection at the University Hospital of Regensburg from November 2008 to April 2017 were retrospectively examined. Due to the design of the study an informed consent was not necessary. Over the first seven days after admission to the ICU, detailed information, e.g. monitoring of blood gas analysis (BGA) and laboratory parameters, was obtained. Anesthesia and surgery protocols, electronic patient files, particularly from the ICU, and physician’s letters were included for data collection.

Surgical management

The operation followed a standardized procedure [9]. After thoracotomy, the heart and aorta were exposed, and blood circulation was carried out with a cardiopulmonary bypass. Hypothermia was induced for cerebral protection. The management of hypothermia did not change over the time. Depending on the length of the dissection, the ascending aorta, ascending aorta with the proximal hemiarch or ascending aorta and the total arch were replaced with a vascular prosthesis. If necessary, the aortic valve was either reconstructed or replaced [10].

Anesthetic and ICU management

Midazolam and/or propofol in combination with sufentanil and pancuronium were mainly used for anesthetic induction. For the maintenance of anesthesia, in general, continuous sufentanil and sevoflurane were given. The ventilation goals were a tidal volume of 6–8 ml kg -1, a respiratory rate of 10–12 min-1 and a positive end-expiratory pressure (PEEP) of ≥ 5 mmHg. Thiopental and/or cortisone were regularly given for cerebral protection during extracorporeal bypass. Patients with a hemoglobin concentration of < 8.0 g dl-1 received blood transfusion.

In general, postoperative care included pressure-controlled protective ventilation, infusions and catecholamine regimes following standards [11]. The main criteria for extubation were adequate gas exchange, the level of consciousness (for example GCS and RASS), normothermia, hemodynamic stability, a positive cough reflex and no significant bleeding.

Patients received either narrow-spectrum or broad-spectrum antibiotics depending on the physician in charge. Narrow-spectrum antibiotic was normally a one day course of cefuroxime and broad-spectrum antibiotic was normally piperacillin/tazobactam for several days. Both were started within the first 24 hours after admission.

Further individual treatment regimes, including positioning of the patient and extracorporeal membrane oxygenation (ECMO) therapy, was also dependent on the physician in charge.

ARD definition

Currently, there is no standardized definition for ARD after acute type A aortic dissection surgery [5, 7, 8, 12]. Therefore, we used the latest Berlin definition for moderate acute respiratory distress syndrome (ARDS) and defined ARD as PaO2/FiO2 (PF ratio) ≤ 200 mmHg in at least four out of six BGA within 48 hours after admission to the ICU [13].

Patients transferred to the intermediate care (IMC) or general ward < 48 hours after admission on the ICU were considered to have a PF ratio > 200 mmHg if the patient did not return to the ICU and/or died. For extubated patients, we used a conversion table to determine the FiO2 [14]. ARD patients with postoperative pleural effusion, hemo-/pneumothorax or pneumonia were not excluded. Patients without ARD were considered NON-ARD.

Statistical analysis

The statistical analysis was performed in cooperation with the Department of Biometry at the Centre for Clinical Studies at the University Hospital Regensburg. The SPSS statistics program 23.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Pre-, intra- and postoperative variables are presented as mean ± standard deviation for normally distributed variables, as the median (interquartile range) for variables with a skewed distribution and as absolute and relative frequencies for categorical variables. Risk factors for the development of ARD in association with the pre- and intraoperative variables were analyzed by using univariable logistic regression models. The odds ratio (OR) and the corresponding 95% confidence interval (95% CI) are presented as effect estimates. Differences in the postoperative variables between ARD and NON-ARD patients as well as between patients who received narrow- and broad-spectrum antibiotics were analyzed by using a Student’s t-test for normally distributed variables, the Mann-Whitney U test for non-normally distributed variables and the χ2 test of independence for categorical data. A p-value < 0.05 was considered statistically significant. No adjustments for multiple testing were made due to the exploratory nature of the study.

Results

Overall, 243 cases were analyzed retrospectively. Forty-two patients were excluded due to death ≤ 48 hours after surgery (n = 15), ECMO therapy ≤ 48 hours after surgery (n = 8), massive intraoperative transfusions (≥ 20 fresh frozen plasma (FFP) and/or ≥ 10 red blood cells (RBCs)) (n = 6) or insufficient documentation of BGAs within the first 48 hours (n = 13). A total of 201 patients were included in this study (Fig 1).

Fig 1. Trial profile.

Fig 1

Flow chart showing the number of excluded patients, the causes of exclusion and the group selection. ARD: acute respiratory dysfunction; ECMO: extracorporeal membrane oxygenation; LCOS: low cardiac output syndrome.

A total of 111 out of 201 (55%) patients met our criteria for ARD, which was the most frequent postoperative complication. The incidence of postoperative respiratory failure changed from year to year; however, a trend along the study period could not be detected. Fig 2 shows the mean PF ratio in the respective groups during the time of observation. Each PF ratio between the ARD and NON-ARD groups was significantly different from the preoperative admission until the seventh postoperative day. The lowest PF ratio occurred within the first 24 hours after surgery. Age (OR = 1.03, p = .031) and body mass index (BMI) (OR = 1.09, p = .017) were found to be significant risk factors for the occurrence of an ARD. Leukocytes, creatine kinase (CK) and other clinical parameters showed no significant predictive value (Table 1). No parameters involved in the intraoperative management revealed a predictive value for the development of ARD (Table 2).

Fig 2. PF ratio throughout hospital stay.

Fig 2

PF ratio [mmHg] is presented as the mean value and standard error of the two groups. ADM: ICU admission; ARD: acute respiratory dysfunction; PRE: preoperative. * ≙ p < 0.05; NON-ARD vs. ARD at day 1–7: at 8, 16 and 24 hours.

Table 1. Preoperative variables.

Variable NON-ARD ARD OR (95% CI) p-value
(n = 90) (n = 111)
Mean age [years] 58.6 ± 13.1 62.6 ± 12.1 1.03 (1.00, 1.05) 0.031*
Male (ref. female) 56 [43] 75 [57] 1.27 (0.71, 2.3) 0.429
BMI [kg/m²] 26.9 ± 3.9 28.4 ± 4.3 1.09 (1.02, 1.17) 0.017*
ASA 3.9 ± 0.4 3.9 ± 0.5 1.05 (0.59, 1.89) 0.865
Arterial hypertension (ref. no) 67 [43] 89 [57] 1.39 (0.71, 2.70) 0.333
Coronary heart disease (ref. no) 8 [42] 11 [58] 1.13 (0.43, 2.93) 0.806
Aneurysm (ref. yes) 18 [51] 17 [49] 1.38 (0.67, 2.87) 0.385
AI (ref. yes) 39 [46] 45 [54] 1.12 (0.64, 1.97) 0.690
Pericardial disease (ref. no) 23 [42] 32 [58] 1.18 (0.63, 2.21) 0.605
Ischemia of the organ (ref. no) 2 [29] 5 [71] 2.08 (0.39, 10.96) 0.390
Ischemia of the limb (ref. no) 10 [38] 16 [62] 1.35 (0.58, 3.13) 0.489
COPD (ref. no) 4 [36] 7 [64] 1.45 (0.41, 5.11) 0.566
Nicotine (ref. no) 17 [38] 28 [62] 1.45 (0.73, 2.86) 0.285
Diabetes mellitus (ref. no) 4 [29] 10 [71] 2.13 (0.65, 7.03) 0.215
Chronic renal insufficiency (ref. yes) 5 [46] 6 [55] 1.03 (0.30, 3.49) 0.963
Neurological complication (ref. yes) 25 [46] 29 [54] 1.09 (0.58, 2.03) 0.793
CRP [mg/L] 5.6 (2.9–41.8) 6.6 (2.9–20.5) 1.00 (0.99, 1.01) 0.753
Leukocytes [/nL] 12.7 ± 4.0 12.7 ± 4.2 1.00 (0.93, 1.07) 0.995
CK [U/L] 104.0 (69.0–169.0) 100.0 (70.0–169.0) 1.00 (1.00, 1.00) 0.368

AI: aortic insufficiency; ARD: acute respiratory dysfunction; ASA: Score of the American Society of Anesthesiologists; BMI: body mass index; CK: creatine kinase; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; Ischemia of the organ: heart, liver or kidney; Neurological complication: includes hemiplegia, paresis, seizure or stroke; Pericardial disease: includes effusion or tamponade.

All data are presented as the mean ± standard deviation, number [row-wise %] or median (IQR = interquartile range).

*: p < 0.05; p-value: logistic regression. Odds ratio (OR) and 95% confidence interval (95% CI).

Table 2. Intraoperative variables.

Variable NON-ARD ARD OR (95% CI) p-value
(n = 90) (n = 111)
Surgical procedure:
 Aortic root replacement 51 [50] 51 [50] reference
 Hemiarch replacement 29 [39] 45 [61] 1.55 (0.85, 2.85) 0.156
 Total arch replacement 10 [42] 14 [58] 1.40 (0.57, 3.44) 0.463
Duration of operation [min] 298 ± 64 297 ± 78 1.00 (1.00, 1.00) 0.945
CPB time [min] 172 ± 50 172 ± 58 1.00 (1.00, 1.01) 0.987
Cross-clamp time [min] 96 ± 34 99 ± 32 1.00 (0.99, 1.01) 0.620
Circulatory arrest time [min] 37 ± 18 40 ± 21 1.01 (0.99, 1.03) 0.395
Cerebral perfusion time [min] 32 ± 21 37 ± 22 1.01 (0.99, 1.03) 0.228
Reperfusion time [min] 61 ± 23 56 ± 20 1.01 (0.99, 1.03) 0.282
Hypothermia:
 deep ≤ 20°C 11 [58] 8 [42] reference
 moderate 20.1–28°C 61 [48] 66 [52] 1.49 (0.56, 3.94) 0.425
 mild 28.1–34°C 5 [56] 4 [44] 1.10 (0.22, 5.45) 0.907
Thiopental (ref. yes) 70 [46] 82 [54] 1.30 (0.67, 2.52) 0.432
Cortisone (ref. no) 26 [41] 37 [59] 1.23 (0.67, 2.25) 0.500
RBC [units] 2.7 ± 2.0 3.1 ± 2.1 1.08 (0.94, 1.24) 0.287
FFP [units] 6.1 ± 3.3 6.7 ± 3.9 1.05 (0.97, 1.14) 0.217
Platelets [units] 2.4 ± 0.9 2.5 ± 1.0 1.06 (0.78, 1.43) 0.713
PCC [units] 3658 ± 1834 3645 ± 1813 1.00 (1.00, 1.00) 0.959

ARD: acute respiratory dysfunction; Cortisone: e.g. prednisolone, dexamethasone; CPB time: cardiopulmonary bypass time; FFP: fresh frozen plasma; PCC: prothrombin complex concentrate; RBC: red blood cells.

All data are presented as the mean ± standard deviation or number [%]. *: p < 0.05; p-value: logistic regression. Odds ratio (OR) and 95% confidence interval (95% CI).

The postoperative variables are presented in Table 3. When compared to NON-ARD patients, ARD patients had a longer median ventilation time (NON-ARD: 2493 (912–6922) [min] vs. ARD: 4695 (1852–8918) [min], p = .006) and a longer ICU stay (NON-ARD: 7.0 ± 6.5 [days] vs. ARD: 8.9 ± 6.5 [days], p = .043). The mortality of ARD patients was lower than the mortality of NON-ARD patients (NON-ARD: 10% (9/90) vs. ARD: 3% (3/111), p = .030). In the NON-ARD group, three out of nine patients died due to cardiac complications, and six patients died due to cerebral complications. In the ARD group, two patients died from cardiac complications and one patient died from cerebral complications. Postoperative complications, such as pericardial effusion or tamponade, atrial fibrillation, hemo-/pneumothorax, pleural effusion, renal and neurological complication, were evenly distributed in both groups. There were a few more cases of pneumonia and tracheotomy in the ARD group than in the NON-ARD group. The blood lactate levels measured on the first postoperative day were significantly higher in the ARD group than in the NON-ARD group (p = .001; Table 3).

Table 3. Postoperative variables.

Variable NON-ARD ARD p-value
(n = 90) (n = 111)
CRP 1 day [mg/L] 91.9 ± 53.8 78.9 ± 51.9 0.101
CRP 2 day [mg/L] 176.4 ± 62.0 167.1 ± 59.1 0.281
Leukocytes 1 day [/nL] 9.9 ± 3.3 10.2 ± 3.4 0.484
Leukocytes 2 day [/nL] 12.4 ± 4.4 12.1 ± 3.9 0.631
CK 1 day [U/L] 599 (339–1068) 512 (333–1354) 0.557
CK 2 day [U/L] 642 (374–1532) 752 (478–1730) 0.357
Lactate 1 day [mg/dL] 20.3 ± 13.5 30.1 ± 26.7 0.001*
Lactate 2 day [mg/dL] 11.5 ± 5.0 13.3 ± 9.2 0.074
Pericardial disease 14 [16] 22 [20] 0.433
Pneumonia 8 [9] 19 [17] 0.089
Hemo-/Pneumothorax 4 [4] 8 [7] 0.411
Pleural effusion 35 [39] 51 [46] 0.315
Tracheotomy 5 [6] 15 [14] 0.061
Ventilation [min] 2493 (912–6922) 4695 (1852–8918) 0.006*
Renal complication 17 [19] 23 [21] 0.746
RRT 13 [14] 20 [18] 0.496
Neurological complication 29 [32] 40 [36] 0.571
Delirium 19 [21] 24 [22] 0.930
ICU stay [days] 7.0 ± 6.5 8.9 ± 6.5 0.043*
Hospital mortality 9 [10] 3 [3] 0.030*

ARD: acute respiratory dysfunction; CK: creatine kinase; CRP: C-reactive protein; ICU stay: intensive care unit stay; Neurological complication: includes hemiplegia, paresis, seizure or stroke; Pericardial disease: effusion or tamponade; Renal complication: renal insufficiency or failure; RRT: renal replacement therapy.

All data are presented as the mean ± standard deviation, number [%] or median (IQR = interquartile range).

*: p < 0.05; p-value: χ2; except for CK and ventilation (Mann-Whitney U test) and CRP, ICU stay, lactate, leukocytes and SAPS (Student’s t-test).

All patients were given antibiotics. A total of 42% of the patients (n = 84) received a narrow-spectrum antibiotic and 58% (n = 117) received a broad-spectrum antibiotic (Fig 3). In the NON-ARD group 43% of the patients (n = 39) were treated with a narrow-spectrum antibiotic and 57% (n = 51) were treated with a broad-spectrum antibiotic. In the ARD group 41% (n = 45) and 59% (n = 66) were treated with a narrow- or a broad-spectrum antibiotic, respectively. Pneumonia cases were equally diagnosed in both groups independently of the applied antibiotic medication (p = .391). In both groups the incidence of postoperative complication was tendentially higher in patients treated with a broad-spectrum antibiotic (Fig 3). In the NON-ARD group neurological complication were significantly more often, while in the ARD group renal complication were significantly more often when treated with a broad-spectrum antibiotic (p < .001 and p = .039). The hospital mortality was highest in the NON-ARD group treated with a broad-spectrum antibiotic (p = .009).

Fig 3. Postoperative outcome and antibiotic treatment.

Fig 3

Comparison of postoperative complications between NON-ARD and ARD which are subdivided in the antibiotic groups. ARD: acute respiratory dysfunction; Neurological complication: includes hemiplegia, paresis, seizure or stroke; Renal complication: renal insufficiency or failure; RRT: renal replacement therapy. * ≙ p < 0.05 (Narrow-spectrum vs. broad-spectrum antibiotic in the NON-ARD and ARD group).

Independently of the ARD and NON-ARD group, patients treated with broad-spectrum antibiotic spent two additional days in the ICU (p = .061) and had a longer median ventilation time (narrow-spectrum antibiotic: 1607 (808–8242) [min] vs. broad-spectrum antibiotic: 4695 (2098–7941) [min], p = .002) compared to patients treated with narrow-spectrum antibiotic. Of all patients that died during their hospital stay 10 out of the 12 patients belonged to the broad-spectrum antibiotic group (p = .069). The choice of antibiotics did not influence the incidence of pneumonia (narrow-spectrum antibiotic: 13% vs. broad-spectrum antibiotic: 14%, p = .905).

Discussion

This retrospective study shows that ARD is the main complication that occurred within 24 hours of acute type A aortic dissection surgery at a university hospital in Germany. The preoperative risk factors for ARD are a higher age and an increased BMI. ARD patients required a longer time of ventilation and an extended stay in the ICU, tended to develop pneumonia more often and needed tracheotomy more frequently than NON-ARD patients. Early broad-spectrum antibiotics did not influence the incidence of pneumonia and did not seem to be advantageous in preventing the development of ARD.

Postoperative ARD is a typical complication after non-cardiac and cardiac surgery [15, 16]. The incidence of ARD after surgery for acute type A aortic dissection is 8–48.5% [5, 7, 8, 12]. The respective studies have usually defined ARD on the basis of the Berlin definition for ARDS [13]. However, the PF ratio and time of measurement differed among all studies. For example, Girdauskas et al. defined ARD as the reduction of the PF ratio < 150 mmHg within 72 hours after surgery. These authors found an ARD incidence of 13% [7]. Chen et al., who defined ARD as a PF ratio < 300 mmHg within 7 days after surgery, reported an incidence of 12.7% [8]. In the present study, the incidence of ARD was higher (55%) than that in previous studies. Obviously, the chosen PF ratio of ≤ 200 mmHg within the observation period of 48 hours after surgery might be the reason that we observed a higher incidence of ARD. Furthermore, the selected inclusion and exclusion criteria might have had a substantial influence on the study results. For example, in the present study, extubated patients were included by using a conversion table to determine the FiO2 for nasal probe and mask ventilation [14]. It is not clear how other studies addressed this issue. Moreover, only patients with early ECMO therapy, massive intraoperative transfusions, early death and insufficient documentation of BGAs were excluded in this study. In contrast, Girdauskas et al. and Chen et al. also excluded patients with cardiogenic pulmonary edema, pneumonia, pulmonary embolism or hemo-/pneumothorax [7, 8]. Interestingly, studies with a comparable definition of ARD and no defined exclusion criteria showed a similar incidence of 48.5% for ARD [12]. Our ARD patients required a longer time of ventilation with an extended stay in the ICU, tended to develop pneumonia and underwent tracheotomy more often than NON-ARD patients. This finding is supported by other studies who had similar results [7, 8, 12].

This study demonstrated that higher age and an increased BMI are risk factors for the development of ARD after acute type A aortic dissection surgery. This result is supported by other studies [12, 17]. Normally, obesity is known as a protective factor against admission to the ICU [18]. The meta-analysis by Ni et al. demonstrated that patients with ARDS and obesity have a lower mortality than non-obese patients [19]. In the present study, ARD patients suffering from obesity died significantly less frequently than NON-ARD patients. But it should not be neglected that it could also be a selection bias due to the ARD definition. In addition, oxygenation impairment, prolonged circulatory arrest time, operative procedures and massive blood transfusion are also risk factors for ARD [12, 16]. The latter was not addressed in our study since patients with intraoperative massive transfusions were excluded from the analysis. A preoperative malperfusion of one or more organs is also associated with the occurrence of ARD [7]. Strikingly, patients with ARD showed a significantly higher lactate concentration–an indirect indicator for malperfusion–on the first postoperative day compared to that in NON-ARD patients in the presented manuscript [20].

After cardiac surgery, especially after aortic surgery, the incidence of ARD is high. Pathophysiological data suggest that systemic inflammation could cause postoperative ARD and is possibly triggered or aggravated by microbial processes [21, 22]. Based on this assumption, treatment with broad-spectrum antibiotics is commonly used early in the ICU. The advantage of this approach has not been demonstrated in the literature at this moment. All patients in our study received an antibiotic treatment. Narrow-spectrum and broad-spectrum antibiotics were equally distributed in the NON-ARD and ARD group. There was no difference in the incidence of pneumonia between the two groups. Although the groups had comparable preoperative demographic and medical characteristics, patients who received a broad-spectrum antibiotic therapy showed a worse postoperative outcome with a higher incidence of renal and neurological complication and death than patients who received narrow-spectrum antibiotics. Piperacillin/tazobactam, which is generally used as a broad-spectrum antibiotic treatment, is not commonly associated with nephrotoxicity [23]. However, it was observed that vancomycin in combination with piperacillin/tazobactam increases the number of acute kidney injuries [24]. Among all of the patients, only 7 out of the 201 patients were treated with this antibiotic combination as an escalation of treatment during their hospital stay. Therefore, the side effects of broad-spectrum antibiotic treatment may only be a minor cause of the renal and neurological symptoms. However, other more potent factors that are not affected by the intensive care treatment might determine the patient outcome. First, an aortic dissection alone can cause kidney and brain malperfusion and damage prior to the surgical intervention or stay in the ICU [25]. However, we do not know which patients experienced malperfusion because this was not documented. Second, the surgical techniques and the cardiopulmonary bypass time associated with circulatory arrest may have led to organ damage [16]. Third, postoperative care with insufficient lung protective ventilation, without the prone position and without restrictive fluid-volume management may have aggravated postoperative respiratory dysfunction [21, 26]. Furthermore, some studies have described a kidney-lung crosstalk. It is assumed that the lungs and kidneys share common pathophysiologic pathways and could thereby damage each other [27]. Accordingly, ARD can affect renal insufficiency or contribute to it. It is also possible that a neurological disorder could have led to silent aspirations and contributed to ARD or pneumonia [28].

Currently, no studies on the prevention of ARD by prophylactic and therapeutic antibiotic treatment after surgery for type A aortic dissection exist. However, Mui et al. conducted a prospective, randomized study on perioperative antibiotic treatment after open appendectomy due to acute non-perforated appendicitis. Patients receiving a 5-day perioperative antibiotic treatment received no benefit compared to that in patients who received a single dose of preoperative antibiotics, whereas longer antibiotic treatment was associated with more postoperative complications [29]. Another randomized study found that in comatose survivors of out-of-hospital cardiac arrest, prophylactic antibiotics did not lead to a better outcome than a clinically-driven antibiotic treatment [30]. Similarly, patients in the present study who received a broad-spectrum, and presumably more effective, antibiotic therapy did not have better postoperative outcomes and had more nephrological and neurological complications than patients who received a narrow-spectrum antibiotic treatment.

The present study has some potential limitations due to its retrospective design. First, our results are based on documented data and are therefore limited in their ability to be compared with those from other studies. Second, the different ARD definitions used in other studies make it difficult to compare their results with each other and with our results; and it might have had an impact on our results. To validate our results and to enhance the power of the study, a multi-centre study would be necessary. Third, the postoperative antibiotic therapy in the present study did not follow a standardized procedure. Although it seems that broad-spectrum antibiotic treatment does not influence the incidence of ARD or the occurrence of pneumonia, due to the design of our study, we cannot rule out that the outcome of this patient group would have been worse without broad-spectrum antibiotic treatment. Fourth, we cannot clarify if the operation technique and cerebral protection has changed over the years. This might have had an impact on the outcome of the patients. Further prospective randomized studies that employ defined standards for antibiotic treatment will be necessary to replicate the effect of prophylactic antibiotic therapy on ARD.

In conclusion, ARD is a common complication in the first 24 hours after acute type A aortic dissection surgery. Higher age and increased BMI were associated with the occurrence of postoperative ARD in our study. Patients who received broad-spectrum antibiotics did not show a lower incidence of pneumonia than patients who received narrow-spectrum antibiotics. Furthermore, patients who received broad-spectrum antibiotics had more postoperative complications.

Data Availability

These data are legally restricted and cannot be shared publicly. Due to the new General Data Protection Regulation (GDPR; EU 2016/679) by the European Union Government, our data protection commissioner recommends that the data from this study, containing potentially identifying or sensitive patient information, are only available upon request. Data are stored on the institutional server at the Department of Anesthesiology at the University of Regensburg. Interested, qualified researchers may request the data by contacting Dr. Michael Gruber at michael.gruber@ukr.de.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Andrea Ballotta

13 Jan 2020

PONE-D-19-32192

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: a retrospective analysis

PLOS ONE

Dear Mrs. Möller,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Feb 27 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

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Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Andrea Ballotta

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

On the basis of the comments of the two reviewers i invite you as authors to revise your manuscript following the concerns and the issues raised up by the two reviewers.

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When submitting your revision, we need you to address these additional requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Tahnk you for your paper.

The paper is interesting because it consider the impact of our antibiotic on the outcome of our patients, despite that in my opinion I think the use of broad spectrum antibiotic is influence non only by the lung status but also from the clinical analysis.

Patients who are going clinically worst need to be covered by broad spectrum non only because the lung problem.

I don't understand how patients who develop ARF can die less then who don't, it might be the selection of ARF definition.

Reviewer #2: The Authors investigated the incidence, risk factors and impact on clinical outcomes of acute respiratory failure after surgery for acute type A aortic dissection. The retrospective cohort spans from 2008 to 2017.

I only have a few comments:

- did surgical techniques and cerebral protection techniques change during the study period?

- most patients were managed with moderate hypothermia. Did this change over time? If so, did this impact on transfusional requirements? Do the Authors believe that this had an impact on respiratory complications?

- did the incidence of postoperative respiratory failure change along the study period?

**********

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Reviewer #1: No

Reviewer #2: Yes: Dr. Fabio Sangalli, MD, FASE

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Feb 11;16(2):e0246724. doi: 10.1371/journal.pone.0246724.r002

Author response to Decision Letter 0


17 Feb 2020

Dear editor and reviewers,

We would like to thank the academic editor Mrs. Balotta and the reviewers for their extensive and constructive review of our manuscript.

We have revised our paper and hope that our careful revision and our respective statements are satisfying. The following is a detailed response to the editors’ and reviewers’ comments.

Editor:

Journal Requirements:

When submitting your revision, we need you to address these additional requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

-> Changes have been made in line 180, 300, 306, 313, 328, 342, 361, 381, 400, and 401.

-> PACE has been used before the first submission.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifyingor sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

-> As we pointed out, the data are legally restricted and cannot be shared publicly. They are available any time upon request by contacting our Department at the University of Regensburg. The head of our research laboratory, Dr. Michael Gruber takes care of a safe data backup.

-> https://www.ukr.de/kliniken-institute/Anaesthesiologie/Klinikteam___Mitarbeiter/Forschungslabor/index.php

Reviewer #1: Tahnk you for your paper.

The paper is interesting because it consider the impact of our antibiotic on the outcome of our patients, despite that in my opinion I think the use of broad spectrumantibiotic is influence non only by the lung status but also from the clinical analysis.

Patients who are going clinically worst need to be covered by broad spectrum non only because the lung problem.

I don't understand how patients who develop ARF can die less then who don't, it might be the selection of ARF definition.

-> Yes you are right, we were also surprised by our results. There might be a selection bias due to the ARD definition. However, other factors might indepently influence the outcome. For example, a recent meta-analysis showed that the body mass index can predict the clinical outcomes for patients with acute respiratory distress syndrome. Ni et al. showed that obesity and morbid obesity was associated with a lower mortality in patients with ARDS. We found a higher BMI in our ARD group. Accordingly, this might have influenced our outcome with a lower mortality. With regard to your very important annotation, we added the following sentence in line 218: “But it should not be neglected that it could also be a selection bias due to the ARD definition.” Furthermore, we revised our sentence in line 274: “Second, the different ARD definitions used in other studies make it difficult to compare their results with each other and with our results; and it might have had an impact on our results.”

Reviewer #2: The Authors investigated the incidence, risk factors and impact on clinical outcomes of acute respiratory failure after surgery for acute type A aortic dissection. The retrospective cohort spans from 2008 to 2017.

I only have a few comments:

- did surgical techniques and cerebral protection techniques change during the study period?

-> This is a very important annotation. It might be comprehensible that over the time period of 9 years a change in the surgical technique and/or cerebral protection might have occurred. Unfortunately, this was not well documented.

-> As we totally agree, we therefore changed the manuscript (line 282): “Fourth, we cannot clarify if the operation technique and cerebral protection has changed over the years. This might have had an impact on the outcome of the patients.”

- most patients were managed with moderate hypothermia. Did this change over time? If so, did this impact on transfusional requirements? Do the Authors believe that this had an impact on respiratory complications?

-> The management of hypothermia did not change over the time. Therefore, transfusional requirements were not different. These results are listed in table 2. To respond to this important annotation, we changed our manuscript (line 66): “The management of hypothermia did not change over the time.”

- did the incidence of postoperative respiratoryfailure change along the study period?

-> This is a very interesting question! We have looked at our data. We found a different incidence of postoperative respiratory failure per year. However, we did not see a trend over the time. Therefore, we changed our manuscript (line 127): “The incidence of postoperative respiratory failure changed from year to year; however, a trend along the study period could not be detected.”

Attachment

Submitted filename: Response to Reviewers_Revision_1.docx

Decision Letter 1

Dong-Xin Wang

4 May 2020

PONE-D-19-32192R1

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: a retrospective analysis

PLOS ONE

Dear Dr. Moeller,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected.

Specifically: the manuscript does not provide any new knowledge. 

I am sorry that we cannot be more positive on this occasion, but hope that you appreciate the reasons for this decision.

Yours sincerely,

Dong-Xin Wang

Academic Editor

PLOS ONE

Additional Editor Comments:

Acute respiratory dysfunction (ARD) is not a widely accepted diagnosis for postoperative pulmonary complications (see Anesthesiology 2010; 113:1338 –50). There are many postoperative pulmonary complications which are usually correlated with each other. For example, respiratory failure may be related to any other respiratory complications; it may also be related to cardiac failure. Furthermore, the severity of postoperative complications are different. A class II or higher on the Clavien-Dindo classification is usually accepted as a complication (see Ann Surg 2009;250: 177–186). The editor encourage the authors to make endpoint diagnosis according to widely accepted criteria. A composite endpoint may be better than a single diagnosis. They should then reanalyze data and resubmit their manuscript after revision. 

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

- - - - -

For journal use only: PONEDEC3

PLoS One. 2021 Feb 11;16(2):e0246724. doi: 10.1371/journal.pone.0246724.r004

Author response to Decision Letter 1


3 Sep 2020

Dear editor and reviewers,

We would like to thank the academic editor Mrs. Balotta and the reviewers for their extensive and constructive review of our manuscript.

We have revised our paper and hope that our careful revision and our respective statements are satisfying. The following is a detailed response to the editors’ and reviewers’ comments.

Editor:

Journal Requirements:

When submitting your revision, we need you to address these additional requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

=> Changes have been made in line 180, 300, 306, 313, 328, 342, 361, 381, 400, and 401.

=> PACE has been used before the first submission.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifyingor sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

=> As we pointed out, the data are legally restricted and cannot be shared publicly. They are available any time upon request by contacting our Department at the University of Regensburg. The head of our research laboratory, Dr. Michael Gruber takes care of a safe data backup.

=> https://www.ukr.de/kliniken-institute/Anaesthesiologie/Klinikteam___Mitarbeiter/Forschungslabor/index.php

Reviewer #1: Tahnk you for your paper.

The paper is interesting because it consider the impact of our antibiotic on the outcome of our patients, despite that in my opinion I think the use of broad spectrumantibiotic is influence non only by the lung status but also from the clinical analysis.

Patients who are going clinically worst need to be covered by broad spectrum non only because the lung problem.

I don't understand how patients who develop ARF can die less then who don't, it might be the selection of ARF definition.

=> Yes you are right, we were also surprised by our results. There might be a selection bias due to the ARD definition. However, other factors might indepently influence the outcome. For example, a recent meta-analysis showed that the body mass index can predict the clinical outcomes for patients with acute respiratory distress syndrome. Ni et al. showed that obesity and morbid obesity was associated with a lower mortality in patients with ARDS. We found a higher BMI in our ARD group. Accordingly, this might have influenced our outcome with a lower mortality. With regard to your very important annotation, we added the following sentence in line 218: “But it should not be neglected that it could also be a selection bias due to the ARD definition.” Furthermore, we revised our sentence in line 274: “Second, the different ARD definitions used in other studies make it difficult to compare their results with each other and with our results; and it might have had an impact on our results.”

Reviewer #2: The Authors investigated the incidence, risk factors and impact on clinical outcomes of acute respiratory failure after surgery for acute type A aortic dissection. The retrospective cohort spans from 2008 to 2017.

I only have a few comments:

- did surgical techniques and cerebral protection techniques change during the study period?

=>This is a very important annotation. It might be comprehensible that over the time period of 9 years a change in the surgical technique and/or cerebral protection might have occurred. Unfortunately, this was not well documented.

=> As we totally agree, we therefore changed the manuscript (line 282): “Fourth, we cannot clarify if the operation technique and cerebral protection has changed over the years. This might have had an impact on the outcome of the patients.”

- most patients were managed with moderate hypothermia. Did this change over time? If so, did this impact on transfusional requirements? Do the Authors believe that this had an impact on respiratory complications?

=>The management of hypothermia did not change over the time. Therefore, transfusional requirements were not different. These results are listed in table 2. To respond to this important annotation, we changed our manuscript (line 66): “The management of hypothermia did not change over the time.”

- did the incidence of postoperative respiratoryfailure change along the study period?

=> This is a very interesting question! We have looked at our data. We found a different incidence of postoperative respiratory failure per year. However, we did not see a trend over the time. Therefore, we changed our manuscript (line 127): “The incidence of postoperative respiratory failure changed from year to year; however, a trend along the study period could not be detected.”

Attachment

Submitted filename: Response to Reviewers_Revision_1 09_2020.docx

Decision Letter 2

Aleksandar R Zivkovic

1 Dec 2020

PONE-D-19-32192R2

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: a retrospective analysis

PLOS ONE

Dear Dr. Möller,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please see below my comments and suggestions regarding the manuscript.

Please submit your revised manuscript by Jan 15 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Aleksandar R. Zivkovic

Academic Editor

PLOS ONE

Journal Requirements:

1. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research

Additional Editor Comments (if provided):

The manuscript has merits to be accepted for the publication, however, I would like to point out the following matters:

Please consider addressing the following major points:

1. It is not clear which criteria were used to make the decision on using extended/broad spectrum antibiotics. Please describe the criteria. In case the criteria are not available/ the decision was made based on the attending clinician’s discretion, this, as well, needs to be described.

2. Please consider including only two patient groups: patients with acute respiratory dysfunction (ARD) and those without (NON-ARD). Furthermore, I would suggest describing the profile and the percentage of patients receiving narrow- or broad spectrum antibiotics within these two groups. Additional subdivision of the patients into the further two groups (based on narrow/broad spectrum antibiotics) could place the results out of focus. The main finding, that the type of the antibiotic regime did not correlate with the occurrence of the ARD, could be better emphasized if the authors focus on the two patient groups and describe the findings accordingly.

Minor points:

1. Line 23: please, introduce (define) the PF ratio: “PaO2/FiO2≤ 200 mmHg (PF ratio) within…”

2. Line 29: please, stay consistent in describing patient groups: first ARD, followed by the NON-ARD (or, alternatively, the other way around), but, please, keep consistency throughout the abstract text.

3. Line 51: please, consider rephrasing the term “certain”.

4. Line 61: Please, rephrase the following: “especially”

5. Line 64: please, remove “commonly”.

6. Line 66: please, consider rephrasing the following sentence: “For cerebral protection hypothermia was induced”

7. Line 77: please, remove “typical”

8. Line 78: please, consider rephrasing the following: “The main criteria for extubation were… the level of consciousness… the ability to follow instructions…” The criterion for the extubation is, presumably, the sufficient level of consciousness (RASS? GCS?), which includes the ability to follow instructions.

9. Line 104: please use “skewed distribution” instead of “skewed distributed”

10. Line 127: it is not clear what was significantly different. Please, rephrase this sentence and include the statistics. Consider pointing out whether the observed difference regards to the groups or the time points of the measurements.

11. Line 149: Please rephrase the term “slightly”

12. Line 172: please, check the sentence: “… than those in the patients treated with…”

13. Line 229: It is not clear whether authors refer to the findings of their study or the current literature regarding the term “at the moment”. Please rephrase.

14. Line 238: please consider rephrasing “… than those of patients who…”

15. Line: 248: “because this was not the focus of our study”. Please rephrase. The reason for not knowing which patients experienced malperfusion might be the fact that the records regarding this information are missing, however, not the fact that the it is “not the focus of the study”.

16. Line 264: please change “did not led” into “did not lead”

17. Line 266: please change “assumingly” into “presumably”. Moreover, consider discussing the option that patients who received broad spectrum antibiotics showed clinically more severe illness than those receiving narrow spectrum antibiotics. Do authors have access to disease severity scores obtained at the ICU (SOFA, APACHE, SAPS, TISS)?

18. Lines 266 and 268: please, consider rephrasing the following: can antibiotic therapy be “more effective”/ “less intensified”?

19. Line 269: please consider rephrasing the first sentence.

20. Line 274: consider using the term: multi-centre study.

21. Line 286: please check: “than that in patients”

22. Line 287: please, remove/change the term “appear”

23. Line 289: please check: “than those in patients”

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Reviewers' comments:

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PLoS One. 2021 Feb 11;16(2):e0246724. doi: 10.1371/journal.pone.0246724.r006

Author response to Decision Letter 2


23 Jan 2021

Dear editor,

We would like to thank the academic editor Mr. Zivkovic for his extensive and constructive review of our manuscript. We have not found any comments from reviewers and are therefore only guided by the comments from the Academic editor.

We have revised our paper and hope that our careful revision and our respective statements are satisfying. The following is a detailed response to the editors’ comments. Our line specifications refer to the “revised manuscript with track changes”.

Editor:

Journal Requirements:

1. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether youobtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

-> With regard to your very important annotation, we added the following sentence in line 62: “Due to the design of the study an informed consent was not necessary.”

Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research

-> The Ethics Statement field of the submission form has been changed.

Additional Editor Comments (if provided):

The manuscript has merits to be accepted for the publication, however, I would like to point out the following matters:

Please consider addressing the following major points:

1. It is not clear which criteria were used to make the decision on using extended/broad spectrum antibiotics. Please describe the criteria. In case the criteria are not available/ the decision was made based on the attending clinician’s discretion, this, as well, needs to be described.

-> Yes, the decision was made by the physician in charge. Line 90: “Patients received either narrow-spectrum or broad-spectrum antibiotics depending on the physician in charge.”

To make the sentence more prominent, it was moved to the end of the section “Anesthetic and ICU management”.

2. Please consider including only two patient groups: patients with acute respiratory dysfunction (ARD) and those without (NON-ARD). Furthermore, I would suggest describing the profile and the percentage of patients receiving narrow- or broad spectrum antibiotics within these two groups. Additional subdivision of the patients into the further two groups (based on narrow/broad spectrum antibiotics) could place the results out of focus. The main finding, that the type of the antibiotic regime did not correlate with the occurrence of the ARD, could be better emphasized if the authors focus on the two patient groups and describe the findings accordingly.

-> Thank you for the valuable comment. We completely agree with you and have therefore made some changes to focus more on the groups NON-ARD and ARD.

Line 24: “All patients received either narrow- or broad-spectrum antibiotics.”

Line 32: “The incidence of pneumonia was independent of the antibiotic treatment regime (p = .391). Renal and neurological complication rate was higher in patients treated with broad-spectrum antibiotic.”

We have deleted the paragraph Classification of antibiotic groups and inserted therefore the sentence (line 90): “Patients received either narrow-spectrum or broad-spectrum antibiotics depending on the physician in charge. Narrow-spectrum antibiotic was normally a one day course of cefuroxime and broad-spectrum antibiotic was normally piperacillin/tazobactam for several days. Both were started within the first 24 hours after admission.”

Lines 167-179 have been rewritten: “In the NON-ARD group 43% of the patients (n = 39) were treated with a narrow-spectrum antibiotic and 57% (n = 51) […]”

Lines 259-263 and 267-271 have also been rewritten.

The sentence in line 324/325 has been deleted.

Supporting information S1 and S2 table has been removed.

Figure 3 has been changed into a new figur.

Minor points:

1. Line 23: please, introduce (define) the PF ratio: “PaO2/FiO2≤ 200 mmHg (PF ratio) within…”

-> The sentence has been corrected: “ARD was defined as PaO2/FiO2 ≤ 200 mmHg (PF ratio) within 48 hours after surgery.”

2. Line 29: please, stayconsistent in describing patient groups: first ARD, followed by the NON-ARD (or, alternatively, the other way around), but, please, keep consistency throughout the abstract text.

-> The abstract has been revised and changes have been made.

3. Line 51: please, consider rephrasing the term “certain”.

-> This has been changed (line 54).

4. Line 61: Please, rephrase the following: “especially”

-> “Especially” has been changed into “particularly” (line 65).

5. Line 64: please, remove “commonly”.

-> We removed the word “commonly” (line 68).

6. Line 66: please, consider rephrasing the following sentence: “For cerebral protection hypothermia was induced”

-> Thank you, the sentence has been rewritten: “Hypothermia was induced for cerebral protection.” (line 70).

7. Line 77: please, remove “typical”

-> The word “typical” has been removed (line 84).

8. Line 78: please, consider rephrasing the following: “The main criteria for extubation were… the level of consciousness… the ability to follow instructions…” The criterion for the extubation is, presumably, the sufficient level of consciousness (RASS? GCS?), which includes the ability to follow instructions.

-> You are absolutely right. In our intensive care unit GCS and RASS is used to determine the level of consciousness. The sentence has been corrected in line 84: “The main criteria for extubation were adequate gas exchange, the level of consciousness (for example GCS and RASS), normothermia, hemodynamic stability, a positive cough reflex and no significant bleeding.”

9. Line 104: please use “skewed distribution”instead of “skewed distributed”

-> This error has been corrected in line 118.

10. Line 127: it is not clear what was significantly different. Please, rephrase this sentence and include the statistics. Consider pointing out whether the observed difference regards to the groups or the time points of the measurements.

-> This is a very important annotation. Therefore, we changed our manuscript (line 140): “Each PF ratio between the ARD and NON-ARD groups was significantly different from the preoperative admission until the seventh postoperative day.”

11. Line 149: Please rephrase the term “slightly”

-> The word has been changed into “a few” (line 162).

12. Line 172: please, check the sentence: “… than those in the patients treated with…”

-> Sentences have been corrected (line 27, line 206, line 216, line 239 and line 245).

13. Line 229: It is not clear whether authors refer to the findings of their study or the current literature regarding the term “at the moment”. Please rephrase.

-> The phrase “in the literature” has been added (line 259).

14. Line 238: please consider rephrasing “… than those of patients who…”

-> The sentence in line 271 has been removed. The sentence in line 302 has been corrected.

15. Line: 248: “because this was not the focus of our study”. Please rephrase. The reason for not knowing which patients experienced malperfusion might be the fact that the records regarding this information aremissing, however, not the fact that the it is “not the focus of the study”.

-> This is absolutely correct. The sentence has been corrected into (line 282): “(…) because this was not documented.”

16. Line 264: please change “did not led” into “did not lead”

-> This error has been corrected (line 298).

17. Line 266: please change “assumingly” into “presumably”. Moreover, consider discussing the option that patients who received broad spectrum antibiotics showed clinically more severe illness than those receiving narrow spectrum antibiotics. Do authors have access to disease severity scores obtained at the ICU (SOFA, APACHE, SAPS, TISS)?

-> “Assumingly” has been changed into “presumably” (line 300).

Unfortunately this was not sufficiently documented.

18. Lines 266 and 268: please, consider rephrasing the following: can antibiotic therapy be “more effective”/ “less intensified”?

-> Thank you. We therefore changed the manuscript (line 299): “Similarly, patients in the present study who received a broad-spectrum, and presumably more effective, antibiotic therapy did not have better postoperative outcomes and had more nephrological and neurological complications than patients who received a narrow-spectrum antibiotic treatment.”

19. Line 269: please consider rephrasing the first sentence.

-> The sentence has been rewritten (line 304): ”The present study has some potential limitations due to its retrospective design.”

20. Line 274: consider using the term: multi-centre study.

-> The word “multi-centre study” has been used (line 309).

21. Line 286: please check: “than that in patients”

-> This has been corrected (line 323).

22. Line 287: please, remove/change the term “appear”

-> The sentence has been deleted (line 325).

23. Line 289: please check: “than those in patients”

-> Thank you. This has been corrected (line 326).

Reviewers' comments:

/

Attachment

Submitted filename: Response to Reviewers_Revision_2.docx

Decision Letter 3

Aleksandar R Zivkovic

26 Jan 2021

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: a retrospective analysis

PONE-D-19-32192R3

Dear Dr. Möller,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Aleksandar R. Zivkovic

Academic Editor

PLOS ONE

Acceptance letter

Aleksandar R Zivkovic

1 Feb 2021

PONE-D-19-32192R3

Postoperative acute respiratory dysfunction and the influence of antibiotics after acute type A aortic dissection surgery: a retrospective analysis

Dear Dr. Möller:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Aleksandar R. Zivkovic

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response to Reviewers_Revision_1.docx

    Attachment

    Submitted filename: Response to Reviewers_Revision_1 09_2020.docx

    Attachment

    Submitted filename: Response to Reviewers_Revision_2.docx

    Data Availability Statement

    These data are legally restricted and cannot be shared publicly. Due to the new General Data Protection Regulation (GDPR; EU 2016/679) by the European Union Government, our data protection commissioner recommends that the data from this study, containing potentially identifying or sensitive patient information, are only available upon request. Data are stored on the institutional server at the Department of Anesthesiology at the University of Regensburg. Interested, qualified researchers may request the data by contacting Dr. Michael Gruber at michael.gruber@ukr.de.


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