# Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries

Galina Dorland, W. Saadat, David M.P. van Meenen, Ary Serpa Neto, Michael Hiesmayr, Markus Hollmann, Gary Mills, Marcos Vidal Melo, Christian Putensen, Werner Schmid, et al.

► To cite this version:

Galina Dorland, W. Saadat, David M.P. van Meenen, Ary Serpa Neto, Michael Hiesmayr, et al. "Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries." Journal of Clinical Anesthesia, 2025, 104, pp.111856. 10.1016/j.jclinane.2025.111856. hal-05072142

HAL Id: hal-05072142

https://hal.science/hal-05072142v1

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Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
Association of preoperative smoking with the occurrence of
postoperative pulmonary complications: A post hoc analysis of an
observational study in 29 countries

Galina Dorland<sup>a,b,*</sup>, W. Saadat<sup>a,b</sup>, David M.P. van Meenen<sup>a,b,c</sup>, Ary Serpa Neto<sup>a,d,e,f,g</sup>, Michael Hiesmayr<sup>h</sup>, Markus W. Hollmann<sup>b,c</sup>, Gary H. Mills<sup>i</sup>, Marcos F. Vidal Melo<sup>j,k</sup>, Christian Putensen<sup>l</sup>, Werner Schmid<sup>h,l</sup>, Paolo Severgnini<sup>m</sup>, Hermann Wrigge<sup>3</sup>, Marcelo Gama de Abreu<sup>124</sup>, Marcus J. Schultz<sup>a,c,h,t,u</sup>, Sabrine N.T. Hemmes<sup>b,v</sup>, for the LAS VEGAS-investigators<sup>125</sup>, Guy Rousseau<sup>124</sup>, Colin Barrett<sup>124</sup>, Lucia Stancombe<sup>124</sup>, Ben Shelley<sup>127</sup>, Helen Scholes<sup>127</sup>, James Limb<sup>127</sup>, Amir Rafi<sup>126</sup>, Lisa Wayman<sup>126</sup>, Jill Deane<sup>126</sup>, David Rogerson<sup>128</sup>, John Williams<sup>129</sup>, Susan Yates<sup>129</sup>, Elaine Rogers<sup>129</sup>, Mark Pulletz<sup>128</sup>, Sarah Moreton<sup>128</sup>, Stephanie Jones<sup>130</sup>, Suresh Venkatesh<sup>130</sup>, Maudrian Burton<sup>129</sup>, Lucy Brown<sup>129</sup>, Cait Goodall<sup>130</sup>, Matthew Rucklidge<sup>131</sup>, Debbie Fuller<sup>132</sup>, Maria Nadolski<sup>132</sup>, Sandeep Kusre<sup>132</sup>, Michael Lundberg<sup>132</sup>, Lynn Everett<sup>133</sup>, Helen Nutt<sup>133</sup>, Maka Zuleika<sup>133</sup>, Peter Carvalho<sup>134</sup>, Deborah Clements<sup>134</sup>, Ben Creagh-Brown<sup>134</sup>, Philip Watt<sup>135</sup>, Parizade Raymode<sup>135</sup>, Rupert Pearse<sup>136</sup>, Otto Mohr<sup>137</sup>, Ashok Raj<sup>137</sup>, Thais Creary<sup>137</sup>, Ahmed Chishti<sup>137</sup>, Andrea Bell<sup>136</sup>, Charley Higham<sup>136</sup>, Alistair Cain<sup>136</sup>, Sarah Gibb<sup>137</sup>, Stephen Mowat<sup>141</sup>, Danielle Franklin<sup>141</sup>, Claire West<sup>141</sup>, Gary Minto<sup>141</sup>, Nicholas Boyd<sup>140</sup>, Gary Mills<sup>138</sup>, Emily Calton<sup>138</sup>, Rachel Walker<sup>139</sup>, Felicity Mackenzie<sup>139</sup>, Branwen Ellison<sup>139</sup>, Helen Roberts<sup>140</sup>, Moses Chikungwa<sup>140</sup>, Clare Jackson<sup>140</sup>, Andrew Donovan<sup>141</sup>, Jayne Foot<sup>141</sup>, Elizabeth Homan<sup>141</sup>, Jane Montgomery<sup>141</sup>, David Portch<sup>141</sup>, Pauline Mercer<sup>141</sup>, Janet Palmer<sup>142</sup>, Jonathan Paddle<sup>142</sup>, Anna Fouracres<sup>142</sup>, Amanda Datson<sup>143</sup>, Alyson Andrew<sup>143</sup>, Leanne Welch<sup>143</sup>, Alastair Rose<sup>143</sup>, Sandeep Varma<sup>143</sup>, Karen Simeson<sup>143</sup>, Mrutyunjaya Rambhatla<sup>143</sup>, Jaysimha Susarla<sup>143</sup>, Sudhakar Marri<sup>143</sup>, Krishnan Kodaganallur<sup>144</sup>, Ashok Das<sup>144</sup>, Shivarajan Algarsamy<sup>145</sup>, Julie Colley<sup>145</sup>, Simon Davies<sup>145</sup>, Margaret Szewczyk<sup>146</sup>, Thomas Smith<sup>146</sup>, Ana Fernandez-Bustamante<sup>146</sup>, Elizabeth Luzier<sup>147</sup>, Angela Almagro<sup>147</sup>, Marcos Vidal Melo<sup>147</sup>, Luiz Fernando<sup>147</sup>, Demet Sulemanji<sup>147</sup>, Juraj Sprung<sup>147</sup>, Toby Weingarten<sup>147</sup>, Daryl Kor<sup>147</sup>, Federica Scavonetto<sup>147</sup>, Yeo Tze<sup>147</sup>, the PROVE Network<sup>2</sup>, the Clinical Trial Network of the European Society of Anaesthesiology

¹LKH Graz, Graz, Austria ²AKH Linz, Linz, Austria ³Medical University Vienna, Austria ⁴UCL - Cliniques Universitaires Saint Luc Brussels, Belgium ⁵Universitary Hospital Brussels (UZ Brussel), Belgium ⁶Het Ziekenhuis Oost Limburg (ZOL), Genk, Belgium ⁷Ghent University Hospital, Gent, Belgium ⁸Maria Middelares, Gent, Belgium ⁹European Society of Anaesthesiology, Brussels, Belgium

Department of Anaesthesiology, Amsterdam UMC, Amsterdam, the Netherlands.

g.dorland@amsterdamumc.nl (G. Dorland).

<footnote>*Corresponding author at:</footnote>

<footnote>E-mail address:</footnote>
1 LKH Graz, Graz, Austria

2 AKH Linz, Linz, Austria

3 Medical University Vienna, Austria

4 UCL - Cliniques Universitaires Saint Luc Brussels, Belgium

5 University Hospital Brussels (UZ Brussel), Belgium

6 Het Ziekenhuis Oost Limburg (ZOL), Genk, Belgium

7 Ghent University Hospital, Gent, Belgium

8 Maria Middelares, Gent, Belgium

9 European Society of Anaesthesiology, Brussels, Belgium

10 General Hospital "prim Dr Abdulah Nakas", Sarajevo, Bosnia and Herzegovina

11 General Hospital Cakovec, Cakovec, Croatia

12 General Hospital Karlovac, Karlovac, Croatia

13 University Clinical Hospital Osijek, Osijek, Croatia

14 University Hospital Rijeka, Rijeka, Croatia

15 General Hospital Dr J Bencevic, Slavonski Brod, Croatia

16 University Hospital Center Split, Split, Croatia

17 University Hospital Merkur, Zagreb, Croatia

18 University Hospital Sveti Duh, Zagreb, Croatia

19 University Hospital, Medical school, "Sestre milosrdnice" (Sister of Charity), Zagreb, Croatia

20 University Hospital Brno, Brno, Czech Republic

21 University Hospital Hradec Kralove, Hradec Kralove, Czech Republic

22 University Hospital Ostrava, Ostrava, Czech Republic

23 Nemocnice Znojmo, Znojmo, Czech Republic
24El Sahel Teaching hospital, Cairo, Egypt

25Kasr Al-Ainy Medical School, Cairo University, Egypt

26Beni Sueif University Hospital, Giza, Egypt

27Fayoum University Hospital, Giza, Egypt

28Suis medical Insurance Hospital, Suis, Egypt

29North Estonia Medical Center, Tallinn, Estonia

30Tartu University Hospital, Tartu, Estonia

31University Hospital of Clermont-Ferrand, Clermont-Ferrand, France

32Institut Hospitalier Franco-Britannique, Levallois-Perret, France

33Saint Eloi University Hospital, Montpellier, France

34Fachkrankenhaus Coswig, Coswig, Germany

35University Hospital Carl Gustav Carus, Dresden, Germany

36Duesseldorf University Hospital, Heinrich-Heine University, Germany

37Diakoniekrankenhaus Friederikenstift, Hannover, Germany

38University of Leipzig, Leipzig, Germany

39"Alexandra" general hospital of Athens, Athens, Greece

40General air force hospital, Athens, Greece

41Aretaieion University Hospital, Athens, Greece

42Attikon University Hospital, Athens, Greece

43Ahepa University Hospital Thessaloniki, Thessaloniki, Greece

44The Lady Davis Carmel Medical Center, Haifa, Israel

45Ospedale San. Paolo Bari, Bari, Italy

46University of Bari "Aldo Moro", Bari, Italy

47Institute for Cancer Research and treatment, Candiolo, Turin, Italy

48Azienda Ospedaliera per l'emergenza Cannizzaro, Catania, Italy

49Ospedale Melegnano, Cernuso, Milano, Italy
50Azienda Ospedaliera – Universitaria Sant'Anna, Ferrara, Italy

51Ospedali Riuniti Di Foggia - University of Foggia, Foggia, Italy

52IRCCS AOU San Martino IST Hospital, University of Genoa, Genoa, Italy

53IRCCS San Raffaele Scientific Institute, Milano, Italy

54Istituto europeo di oncologia – ieo, Milano, Italy

55Ospedale Niguarda Ca'Granda Milano, Milano, Italy

56Ospedale San Paolo - University of Milano, Milano, Italy

57University of Naples "Federico II" Naples, Italy

58Policlinico "P. Giaccone", Palermo, Italy

59Azienda Ospedaliero-Universitaria, Parma, Italy

60Santa Maria degli Angeli, Pordenone, Italy

61Ospedale Misericordia e Dolce - Usl4 Prato, Prato, Italy

62University hospital of Sassari, Sassari, Italy

63Insubria University, Varese, Italy

64Distric hospital Gjakova, Gjakove, Republic of Kosovo

65University Clinical Center of Kosova, Prishtina, Republic of Kosovo

66Regional Hospital "Prim.Dr. Daut Mustafa", Prizren, Republic of Kosovo

67Medical University Hospital, Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania

68Vilnius University Hospital - Institute of Oncology, Vilnius, Lithuania

69Vilnius University Hospital - Santariskiu Clinics, Vilnius, Lithuania

70Mater Dei Hospital, Msida, Malta

71Academic Medical Centre, University of Amsterdam, the Netherlands

72VU University Medical Center, Amsterdam, the Netherlands

73MC Haaglanden, Den Haag, the Netherlands

74Westfries gasthuis, Hoorn, the Netherlands

75Haukeland University Hospital, Bergen, Norway

76Førde Central Hospital/Førde Sentral Sykehus, Førde, Norway
77Martina Hansens Hospital, Gjettum, Norway

78Bærum Hospital, Vestre Viken, Rud, Norway

79Stavanger University Hospital, Stavanger, Norway

80Hospital Santo Tom'as, Panama, Panama

81Hospital do Espírito Santo - 'Evora, E.P.E, 'Evora, Portugal

82Centro Hospitalar de Lisboa Central, E.P.E, Lisboa, Portugal

83Centro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de S. Francisco Xavier, Lisboa, Portugal

84Santarem Hospital, Santarem, Portugal

85Spital Orasenesc, Bolintin Vale, Romania

86Clinical Emergency Hospital of Bucharest, Bucharest, Romania

87Elias University Emergency Hospital, Bucharest, Romania

88Emergency Institute of Cardiovascular Diseases Inst. "Prof. C. C. Iliescu", Bucharest, Romania

89Fundeni Clinical institute - Anaesthesia and Intensive Care, Bucharest, Romania

90Fundeni Clinical institute - Intensive Care Unit, Bucharest, Romania

91Hospital Profesor D Gerota, Bucharest, Romania

92Constanta County Emergency Hospital, Constanta, Romania

93University Emergency County Hospital Targu Mures, Targu Mures, Romania

94Krasnoyarsk State Medical University, Krasnoyarsk, Russia

95Burdenko Neurosurgery Institute, Moscow, Russia

96Moscow Regional Research Clinical Institute, Moscow, Russia

97Municipal Clinical Hospital 7, Moscow, Russia

98Reanimatology Research Institute n.a. Negovskij RAMS, Moscow, Russia

99Clinical Center of Vojvodina, Emergency Center, Novisad, Serbia

100National Cancer Institute, Bratislava, Slovakia

101F.D. Roosevelt teaching Hospital, Banska Bystrica, Slovakia

102Faculty Hospital Nov'e Z'e Z'amky, Nov'amky, Slovakia

103Institute of Oncology Ljubljana, Ljubljana, Slovenia
104University Medical Centre Ljubljana, Ljubljana, Slovenia

105Hospital Sant Pau, Barcelona, Spain

106Hospital Universitari Germans Trias I Pujol, Barcelona, Spain

107University of Navarra, Pamplona, Spain

108Corporacion Sanitaria Parc Tauli, Sabadell, Spain

109Consorcio Hospital General Universitario de Valencia, Valencia, Spain

110Hospital Clinico Valencia, Valencia, Spain

111Hospital Universitario Rio Hortega, Valladolid, Spain

112Central Hospital in Kristianstad, Sweden

113Ufuk University Hospital Ankara, Ankara, Turkey

114Akdeniz University Hospital, Antalya, Turkey

115Istanbul University, Istanbul medical faculty, Istanbul, Turkey

116Acibadem University, Istanbul, Turkey

117Maltepe University, Istanbul, Turkey

118Dokuz Eylül Universitesi Tip Fakültesi, Izmir, Turkey

119Sifa University Hospital, Izmir, Turkey

120Selcuk University faculty of medicine, Konya, Turkey

121Fatih Sultan Mehmet Eğitim Ve Aras, tirma Hastanesi, Istanbul, Turkey

122Institute of Surgery And Transplantology, Kiev, Ukraine

123Zaporizhzhia State Medical University, Zaporizhzhia, Ukraine

124Northern Devon Healthcare NHS Trust, Barnstaple, United Kingdom

125Golden Jubilee National Hospital, Clydebank, Scotland, United Kingdom

126Darlington Memorial Hospital, County Durham and Darlington Foundation NHS Trust, Darlington, United Kingdom

127Royal Derby Hospital, Derby, United Kingdom

128Dorset County Hospital, Dorchester, United Kingdom

129The Princess Alexandra NHS Hospital Trust, Essex, United Kingdom

130Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
131 Hospital James Paget University Hospital NHS Foundation Trust, Great Yarmouth, United Kingdom

132 Royal Surrey County Hospital NHS Foundation Trust, Guildford, United Kingdom

133 Kettering General Hospital NHS Foundation Trust, Kettering, United Kingdom

134 Barts Health NHS Trust, Royal London Hospital, London, United Kingdom

135 Newcastle Upon Tyne Hospitals NHS Trust The Freeman Hospital High Heaton, Newcastle upon Tyne, United Kingdom

136 Derriford Hospital Plymouth Hospitals NHS Trust, Plymouth, United Kingdom

137 Royal Hallamshire Hospital, Sheffield, United Kingdom

138 Mid Staffordshire NHS, Stafford, United Kingdom

139 Musgrove Park Hospital, Taunton, United Kingdom

140 South Devon Healthcare NHS Foundation Trust/Torbay Hospital, Torquay, Torbay, United Kingdom

141 Royal Cornwall Hospital, Truro, United Kingdom

142 Mid Yorkshire Hospitals NHS Trust; Pinderfields Hospital, Wakefield, United Kingdom

143 Sandwell and West Birmingham NHS Trust, West Bromich, United Kingdom

144 York Teaching Hospitals NHS Foundation Trust, York, United Kingdom

145 University of Colorado School of Medicine/University of Colorado Hospital, Aurora, United States

146 Massachusetts General Hospital, Boston, United States

147 Mayo Clinic, Rochester, United States

a Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, the Netherlands

b Department of Anaesthesiology, Amsterdam University Medical Center, Amsterdam, the Netherlands

c Department of Intensive Care & Laboratory of Experimental Intensive Care and Anaesthesiology (L·E·I·C·A), Amsterdam University Medical Center, Amsterdam, the Netherlands

d Department of Critical Care Medicine, Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Australia

e Department of Intensive Care, Austin Hospital, Melbourne, Australia

f Department of Critical Care, Melbourne Medical School, Austin Hospital, University of Melbourne, Melbourne, Australia

g Department of Critical Care, oitspal Israelita in Albert Einsten Sao Paulo, Brazil

h Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, Department of Special Anaesthesia and Pain Therapy, Medical University of Vienna, Vienna, Austria
iOperating Services, Critical Care and anaesthesia, Sheffield Teaching Hospitals, University of Sheffield, Sheffield, UK

jDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA

kDepartment of Anaesthesiology, Columbia University, NY, USA

lDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany

mDepartment of Biotechnologies and Sciences of Life, ASST Sette Laghi, Anestesia Rianimazione Cardiologica, University of Insubria, Varese, Italy

nDepartment of Anaesthesiology, Intensive Care Medicine and Emergency Medicine, Pain Therapy, Bermannstrost Hospital Halle, Halle, Germany

oMedical Faculty, MartinLutherUniversity of HalleWittenberg, Halle, Germany

pDepartment of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, Medical Faculty, University Hospital Carl Gustav Carus, Dresden, Germany

qDepartment of Intensive Care and Resuscitation, Cleveland Clinic, Cleveland, OH, USA

rDepartment of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA

sDepartment of Cardiothoracic Anaesthesia, Cleveland Clinic, Cleveland, OH, USA

tMahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand

uNuffield Department of Medicine, University of Oxford, Oxford, UK

vDepartment of Anaesthesiology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, the Netherlands
HIGHLIGHTS

* Smoking is not associated with overall postoperative pulmonary complications in at-risk patients.

* Respiratory failure was more common in smokers than non-smokers.

* Length of hospital stay and mortality were similar between smokers and non-smokers.

* Propensity score matching did not change the findings.

Keywords:

AnaesthesiaIntraoperative ventilation Smoking Postoperative outcome Postoperative pulmonary complications
PPCs Respiratory complications

<footnote n="1">¹For full list of SWARM contributors please see www.ukswarm.com.</footnote>

<footnote n="2">²PROtective VEntilation Network (www.provenet.eu).</footnote>

<footnote n="3">³LAS VEGAS, ‘Local ASsessment of Ventilatory management during General Anaesthesia for Surgery’.</footnote>
# ABSTRACT

**Introduction:**

While smoking has been consistently identified as a significant contributor to postoperative com-plications, the existing literature on its association with postoperative pulmonary complications remains conflicting.

**Aim:**

We examined the association of preoperative smoking with the occurrence of postoperative pulmonary complications (PPCs).

**Methods:**

Post hoc analysis of an observational study in 146 hospitals across 29 countries. We included patients at increased risk of PPCs, according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (≥26 points). The primary endpoint was the occurrence of one or more predefined PPCs in the first five post-operative days, including unplanned postoperative need for supplementary oxygen, respiratory failure, unplanned need for invasive ventilation, ARDS, pneumonia and pneumothorax. Secondary endpoints included length of hospital stay and in-hospital mortality. We performed propensity score matching to correct for factors with a known association with postoperative outcomes.

**Results:**

Out of 2632 patients, 531 (20.2 %) were smokers and 2102 (79.8 %) non-smokers. At five days after surgery, 101 (19.0 %) smokers versus 404 (19.2) non-smokers had developed one or more PPCs (*P* =0.95). Respiratory failure was more common in smokers (5.1 %) than non-smokers (3.0 %) (*P* =0.02), while rates of other PPCs like need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups. Length of hospital stay and mortality was not different between groups. Propensity score matching did not change the findings.

**Conclusion:**

The occurrence of PPCs in smokers is not different from non-smokers.
## Funding:

This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anaesthesiology through their Clinical Trial Network and the Amsterdam University Medical Centers, Amsterdam, The Netherlands.

## Registration:

LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223).

## Prior presentation:

Preliminary study results have been presented at the Euroanaesthesia 2024 International Congress, in Munich, Germany.
# 1.Introduction

Smoking is considered a risk factor in surgical patients, and contributor to the development of postoperative complications. Indeed, surgical site infection and other postoperative complications have been reported to occur more often in smokers, and to be associated with increased general morbidity, longer duration of hospital stay, and more intensive care unit admissions [1]. However, the literature is conflicting with regard to the association of preoperative smoking with post-operative pulmonary complications (PPCs). While some studies have indicated smokers to be at a higher risk of developing PPCs compared to non-smokers [2,3], others found no association of smoking with the occurrence of PPCs [4,5], and one study suggested that the effect may depend on the specific surgical procedure [6]. Consequently, the impact of preoperative smoking on PPCs remains unclear.

PPCs present significant challenges in surgical care, leading to increased morbidity, mortality and healthcare costs [7,8]. In recent years, perioperative practices have advanced significantly, raising the question of whether smoking still has a notable impact on PPCs under current practices. In patients at increased risk of PPCs, the presence of other comorbidities and risk factors may also influence outcomes, potentially moderating the effect of smoking.

Therefore, the aim of this analysis was to assess the association of preoperative smoking with the occurrence of PPCs in patients. Herein we focused on patients at an increased (i.e. intermediate or high) risk for PPCs. We tested the hypothesis, that preoperative smoking has no as-sociations with the occurrence of PPCs, using the dataset of the conve-niently sized worldwide prospective observational ‘Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ (LAS VEGAS) study [9].

# 2.Methods

## 2.1.Study design

This is a post hoc analysis of LAS VEGAS, a worldwide, multicentre, prospective observational study, describing the incidence of patients with increased risk of PPCs, intraoperative ventilation practice and associations between ventilatory parameters and postoperative outcomes. The LAS VEGAS study protocol was first approved by the institutional review board of the Academic Medical Center, Amsterdam, The Netherlands (W12_190#12.17.0227), and thereafter by the institutional review boards of each participating centre. If required, written informed consent from the patient or their legal representative was obtained. The study was registered at clinicaltrials.gov(NCT01601223). We report in compliance with the current guidelines and the recommendations of STrengthening the Reporting of Observational studies in Epidemiology (STROBE) statement (available at: www.strobe-statement.org) (Supplementary Table S1).

## 2.2.Patients

LAS VEGAS enrolled patients in 146 hospitals across 29 countries over a consecutive period of seven days in 2013. National coordinators selected the exact period during which data were collected for the study in their respective countries. Consecutive patients receiving invasive ventilation, via endotracheal tube or supraglottic device during general anaesthesia for elective and non-elective surgical procedures were eligible. Patients under the age of 18, those scheduled for pregnancy-related surgeries, procedures conducted outside the operating room or interventions involving cardiopulmonary bypass were excluded from LAS VEGAS.
For this current analysis, we limited inclusion to patients at increased (i.e. intermediate or high) risk of PPCs with an ‘Assess Respiratory Risk in Surgical Patients in Catalonia’ (ARISCAT) score above 26 points (Supplementary Table S2) [4]. We also applied additional exclusion criteria, as follows. We excluded patients that had received mechanical ventilation in the 30 days prior to surgery, undergoing thoracic surgery or one-lung ventilation, as well as patients with incomplete data on the preoperative smoking status, patients with missing ARISCAT scores, and patients with missing data for the primary endpoint.

### 2.3. Data collected

From the LAS VEGAS database the following variables were used: baseline characteristics including sex, age, body weight and height, ARISCAT score, American Society of Anesthesiologists (ASA) score, smoking status, functional status, coexisting comorbidities such as heart failure, chronic obstructive pulmonary disease, obstructive sleep apnoea syndrome (OSAS), active cancer, chronic kidney failure, liver cirrhosis, neuromuscular disease; risk factors for developing PPCs including preoperative saturation of peripheral oxygen (SpO2), respiratory infection within the past month, preoperative anemia, type of surgical incision and emergency procedure. In LAS VEGAS, ventilation data were collected hourly after induction of anaesthesia and start of invasive ventilation until tracheal extubation, including tidal volume (VT), positive end-expiratory pressure (PEEP), plateau (Pplat), peak airway pressure (Ppeak), fraction of inspired oxygen (FiO2) and respiratory rate (RR).

### 2.4. Patient classification

Preoperative smoking was categorized into smokers and non-smokers. In LAS VEGAS, the smoking status was obtained from the preoperative patient records.

### 2.5. Endpoints

The primary endpoint of this analysis was occurrence of PPCs in the first five postoperative days, defined as a composite binary endpoint comprising six individual PPCs. Patients who develop at least one PPC were considered as meeting the primary endpoint. In the primary endpoint, PPCs weighted equally. Secondary endpoints included the occurrence of the individual PPCs, length of hospital stay, and in-hospital mortality.

### 2.6. Definitions

The composite binary endpoint of PPCs comprised the following previously described conditions: unplanned supplementary oxygen (oxygen administered due to PaO2 <8kPa or SpO2 <90 % in room air, but excluding oxygen supplementation given as standard care, e.g. directly after arrival in the post anaesthetic care unit), respiratory failure (PaO2 <8 kPa or SpO2 <90 % despite oxygen therapy, or a need for non-invasive positive pressure ventilation (NIPPV); unplanned new or prolonged invasive mechanical ventilation (after discharge from the operating room); acute respiratory distress syndrome (ARDS) according to the Berlin criteria [10]; pneumonia (using clinical and laboratory data) and pneumothorax (observed in the chest radiograph). Secondary endpoints comprised of the individual PPCs, categorized based on their severity, wherein unplanned supplemental oxygen was classified as ‘mild’ and the PPCs as ‘severe’ [11].
## 2.7. Calculations

VT was expressed in ml per kg predicted body weight (PBW). PBW was calculated by the following formulas: in females, $45.5 + (0.91 \times \text{height [cm]} - 152.4))$ and in males, $50 + (0.91 \times \text{height [cm]} - 152.4))$. Driving pressure ($\Delta P$) was calculated by $\Delta P = P_{plat} - PEEP$ (in volume-controlled ventilation) or $\Delta P = P_{max} - PEEP$ (in pressure-controlled ventilation).

## 2.8. Sample size

No formal sample size calculation was conducted for this analysis; instead, the number of eligible patients in the LAS VEGAS database determined the sample size. A post hoc power calculation was performed for the primary endpoint.

## 2.9. Statistical analysis

Patients were stratified into two groups based on their preoperative smoking status. Demographic, baseline characteristics and outcome variables are presented as medians and interquartile ranges in case of continuous variables and categorical variables are presented as numbers and percentages. Groups were compared using the Mann-Whitney *U* test for continuous variables and the Fisher exact or Chi-square tests for categorical variables. No assumptions for missing data were made. Length of hospital stay and in-hospital death was censored at postoperative day 28.

The incidence of total, mild or severe PPCs in smokers and non-smokers was compared using Fisher's exact test. As one sensitivity analysis, we performed a propensity score matching to control for potentially confounding factors that could have affected outcomes. Patients were matched according to age, ARISCAT score and functional status using a one-to-one nearest neighbour algorithm without replacement. Variables included in the propensity score model were selected based on clinical relevance and baseline imbalance, as indicated by standardized mean differences (SMDs). Variables with an SMD $\ge 0.1$ were initially considered, with final selection based on clinical relevance i.e. with a known association with PPCs. Variables standardized mean differences were visualized in a LOVE plot and used to assess matching performance. No correction for multiple testing was performed as this analysis was considered to be exploratory.

All analyses were performed in R version 4.2.1 (Core Team, Vienna, Austria, 2021). A *P* value less than 0.05 was considered statistically significant.
<figure><img src="image_2.png" /><figcaption>Fig. 1. CONSORT flowchart.</figcaption></figure>

## 3. Results

### 3.1. Patients

Out of 9864 patients present in the LAS VEGAS database, 2803 (28.4 %) patients were at an increased risk of PPCs as defined by an ARISCAT score ≥ 26 points (Fig. 1). A total of 171 patients were excluded for other reasons as mentioned in the flow chart. Out of the remaining 2632 patients, 531 (20.2 %) patients were smokers and 2102 (79.8 %) were non-smokers. Compared to non-smokers, smokers were generally younger, predominantly male, more often at intermediate risk for PPCs according to the ARISCAT score, had a lower BMI, a higher incidence of respiratory infections within 30 days before surgery, were more frequently
independent functional state, and had higher rates of chronic obstructive pulmonary disease (COPD) and liver cirrhosis but a lower incidence of heart failure (Table 1). Smokers more often underwent vascular and aortic surgeries, while gynecologically and transplant surgeries were less common among them, with intraoperative characteristics being comparable between smokers and non-smokers (Table 2).

**3.2. Occurrence of PPCs**

The overall incidence of PPCs did not differ between smokers and non-smokers. At 5 days after surgery, 101 (19.0 %) smokers versus 404 of 2101 non-smokers (19.2 %) had developed one or more PPCs (P = 0.95) (Fig. 2, Table 3). Respiratory failure was more common in smokers (5.1 %) than non-smokers (3.0 %) (P = 0.02), while rates of other PPCs such as need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups.

**3.3. Length of hospital stay and in-hospital mortality**

Length of hospital stay and in-hospital mortality were not different between smokers and non-smokers (Table 3).

**3.4. Post hoc power and sensitivity analysis**

Propensity score matching did not change the findings (Tables 1, 2, 3 and Fig. 3). Considering that the total PPC incidence in smokers is 20 % and in non-smokers 10.4 % [9,12,13], with an unmatched cohort sample size of 2632 patients, with an $\alpha$ of 0.05, and a smoker to non-smoker ratio of 0.25, the post hoc power analysis showed that we had 99 % power to detect this difference.

# 4. Discussion

The main findings of this post hoc analysis in a prospective cohort of patients receiving intraoperative ventilation during general anaesthesia for surgery and at increased (i.e. intermediate or high) risk for PPCs can be summarized as follows: [1] the overall occurrence of PPCs did not differ between smokers compared to non-smokers; [2] regarding individual PPCs, respiratory failure occurred more frequently among current smokers compared to non-smokers; and [3] there were no differences in length of hospital stay and in-hospital mortality.

Our findings are consistent with those of previous studies, where no association between smoking and postoperative outcomes was found [4,5,14]. Several potential factors could have contributed to the absence of overall difference in PPCs between smokers and non-smokers in our cohort. First, the association between preoperative smoking status and outcomes in patients at increased risk for PPCs has not been extensively studied yet. Patients with higher ARISCAT scores often present with pre-existing comorbidities, which could already predispose them to a heightened risk of respiratory complications irrespective of their smoking status. Additionally, increased risk patients are likely to receive more intensive perioperative care and monitoring aimed
at reducing their elevated risk for PPCs. Consequently, in this increased risk population, the additional risk from smoking may be less evident.

<table><caption>**Table 1**

Patient characteristics unmatched and matched cohorts.</caption><thead><tr><th rowspan="2"></th><th colspan="3">Unmatched cohort</th><th colspan="3">Matched cohort</th></tr><tr><th>Smoker<br>N = 531</th><th>Non-smoker<br>N = 2101</th><th>SMD</th><th>Smoker<br>N = 520</th><th>Non-smoker<br>N = 520</th><th>SMD</th></tr></thead><tbody><tr><td>Age, years, median [IQR]</td><td>56 [46-65]</td><td>64 [52-73]</td><td>0.45</td><td>56 [46-64]</td><td>57 [46-66]</td><td>0.09</td></tr><tr><td>Male sex, n (%)</td><td>340 (64.0)</td><td>936 (44.6)</td><td>0.40</td><td>335 (64.4)</td><td>204 (39.2)</td><td>0.52</td></tr><tr><td>BMI, kg/m<sup>2</sup>, median [IQR]</td><td>26.0 [23.2-29.7]</td><td>27.0 [23.9-30.9]</td><td>0.16</td><td>26.2 [23.2-29.8]</td><td>27.6 [24.2-32.0]</td><td>0.24</td></tr><tr><td>ARISCAT score, median [IQR]</td><td>34 [31-41]</td><td>34 [31-41]</td><td>0.11</td><td>34 [31-41]</td><td>34 [31-34]</td><td>0.00</td></tr><tr><td>ARISCAT group, n (%)</td><td></td><td></td><td>0.12</td><td></td><td></td><td>0.00</td></tr><tr><td>Intermediate (26-44)</td><td>459 (86.4)</td><td>1725 (82.1)</td><td></td><td>453 (87.1)</td><td>453 (87.1)</td><td></td></tr><tr><td>High (&gt;44)</td><td>72 (13.6)</td><td>376 (17.9)</td><td></td><td>67 (12.9)</td><td>67 (12.9)</td><td></td></tr><tr><td>Preoperative SpO<sub>2</sub>, n (%)</td><td></td><td></td><td>0.04</td><td></td><td></td><td>0.01</td></tr><tr><td>≥ 96 %</td><td>316 (66.0)</td><td>1267 (65.9)</td><td></td><td>313 (66.2)</td><td>308 (65.7)</td><td></td></tr><tr><td>91-95 %</td><td>145 (30.3)</td><td>567 (29.5)</td><td></td><td>143 (30.2)</td><td>143 (30.5)</td><td></td></tr><tr><td>&lt; 91 %</td><td>18 (3.8)</td><td>89 (4.6)</td><td></td><td>17 (3.6)</td><td>18 (3.8)</td><td></td></tr><tr><td>Respiratory infection (&lt;30d), n (%)</td><td>73 (13.7)</td><td>166 (7.9)</td><td>0.18</td><td>67 (12.9)</td><td>57 (11.0)</td><td>0.06</td></tr><tr><td>Preoperative anemia, n (%)</td><td>49 (9.8)</td><td>207 (10.4)</td><td>0.02</td><td>44 (9.0)</td><td>36 (7.5)</td><td>0.06</td></tr><tr><td>Surgical incision, n (%)</td><td></td><td></td><td>0.06</td><td></td><td></td><td>0.04</td></tr><tr><td>Peripheral</td><td>130 (24.5)</td><td>456 (21.7)</td><td></td><td>396 (76.2)</td><td>404 (77.7)</td><td></td></tr><tr><td>Abdominal</td><td>401 (75.5)</td><td>1645 (78.3)</td><td></td><td>124 (23.8)</td><td>116 (21.3)</td><td></td></tr><tr><td>Condition surgery, n (%)</td><td></td><td></td><td>0.08</td><td></td><td></td><td>0.08</td></tr><tr><td>Elective</td><td>438 (82.5)</td><td>1789 (85.1)</td><td></td><td>430 (82.7)</td><td>444 (85.4)</td><td></td></tr><tr><td>Urgency</td><td>62 (11.7)</td><td>216 (10.3)</td><td></td><td>61 (11.7)</td><td>54 (10.4)</td><td></td></tr><tr><td>Emergency</td><td>31 (5.8)</td><td>96 (4.6)</td><td></td><td>29 (5.6)</td><td>22 (4.2)</td><td></td></tr><tr><td>Planned duration of surgery, n (%)</td><td></td><td></td><td>0.01</td><td></td><td></td><td>0.05</td></tr><tr><td>&lt;2 h</td><td>111 (20.9)</td><td>467 (22.2)</td><td></td><td>111 (21.3)</td><td>114 (21.9)</td><td></td></tr><tr><td>2-3 h</td><td>246 (46.3)</td><td>905 (43.1)</td><td></td><td>238 (45.8)</td><td>245 (47.1)</td><td></td></tr><tr><td>&gt;3 h</td><td>174 (32.8)</td><td>729 (34.7)</td><td></td><td>171 (32.9)</td><td>161 (31.0)</td><td></td></tr><tr><td>ASA physical status classification, n (%)</td><td></td><td></td><td>0.09</td><td></td><td></td><td>0.17</td></tr><tr><td>I</td><td>77 (14.5)</td><td>285 (13.6)</td><td></td><td>77 (14.8)</td><td>99 (19.1)</td><td></td></tr><tr><td>II</td><td>264 (49.7)</td><td>974 (46.5)</td><td></td><td>260 (50.0)</td><td>254 (48.9)</td><td></td></tr><tr><td>III</td><td>168 (31.6)</td><td>741 (35.4)</td><td></td><td>162 (31.2)</td><td>156 (30.1)</td><td></td></tr><tr><td>IV</td><td>21 (4.0)</td><td>91 (4.3)</td><td></td><td>20 (3.8)</td><td>10 (1.9)</td><td></td></tr><tr><td>V</td><td>1 (0.2)</td><td>3 (0.1)</td><td></td><td>1 (0.2)</td><td>0 (0.0)</td><td></td></tr><tr><td>Functional status, n (%)</td><td></td><td></td><td>0.14</td><td></td><td></td><td>0.00</td></tr><tr><td>Independent</td><td>479 (90.2)</td><td>1798 (85.6)</td><td></td><td>475 (91.3)</td><td>475 (91.3)</td><td></td></tr><tr><td>Partially dependent</td><td>44 (8.3)</td><td>259 (12.3)</td><td></td><td>39 (7.5)</td><td>39 (7.5)</td><td></td></tr><tr><td>Totally dependent</td><td>8 (1.5)</td><td>43 (2.0)</td><td></td><td>6 (1.2)</td><td>6 (1.2)</td><td></td></tr><tr><td>Comorbidities, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Heart failure</td><td>33 (6.2)</td><td>218 (10.4)</td><td>0.15</td><td>31 (6.0)</td><td>39 (8)</td><td>0.06</td></tr><tr><td>COPD</td><td>105 (19.8)</td><td>147 (7.0)</td><td>0.38</td><td>101 (19.4)</td><td>28 (5)</td><td>0.43</td></tr><tr><td>OSAS</td><td>17 (3.2)</td><td>51 (2.4)</td><td>0.04</td><td>16 (3.1)</td><td>17 (3)</td><td>0.01</td></tr><tr><td>Chronic kidney failure</td><td>24 (4.5)</td><td>136 (6.5)</td><td>0.08</td><td>22 (4.2)</td><td>22 (4.2)</td><td>0.00</td></tr><tr><td>Liver cirrhosis</td><td>17 (3.2)</td><td>25 (1.2)</td><td>0.14</td><td>17 (3)</td><td>7 (1.3)</td><td>0.13</td></tr><tr><td>Neuromuscular disease</td><td>3 (0.6)</td><td>18 (0.9)</td><td>0.03</td><td>3 (0.6)</td><td>5 (1.0)</td><td>0.04</td></tr><tr><td>Active cancer</td><td>41 (7.7)</td><td>216 (10.3)</td><td>0.09</td><td>39 (8)</td><td>42 (8.1)</td><td>0.02</td></tr><tr><td>Preoperative red blood cell transfusion, n (%)</td><td>12 (2.3)</td><td>47 (2.2)</td><td>0.00</td><td>10 (1.9)</td><td>7 (1.3)</td><td>0.05</td></tr><tr><td>Units of red blood cells transfused, median [IQR]</td><td>2 [1-2.5]</td><td>2 [1.5-2]</td><td>0.03</td><td>2 [1-2]</td><td>2 [1-2]</td><td>0.07</td></tr><tr><td>Surgical procedure, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Lower GI</td><td>101 (19.0)</td><td>470 (22.4)</td><td>0.08</td><td>97 (18.7)</td><td>112 (21.5)</td><td>0.07</td></tr><tr><td>Upper GI</td><td>126 (23.7)</td><td>440 (20.9)</td><td>0.07</td><td>125 (24.0)</td><td>101 (19.4)</td><td>0.11</td></tr><tr><td>Vascular</td><td>31 (5.8)</td><td>68 (3.2)</td><td>0.13</td><td>30 (5.8)</td><td>14 (2.7)</td><td>0.15</td></tr><tr><td>Aortic</td><td>15 (2.8)</td><td>30 (1.4)</td><td>0.10</td><td>15 (2.9)</td><td>6 (1.2)</td><td>0.12</td></tr><tr><td>Neurosurgery</td><td>20 (3.8)</td><td>84 (4.0)</td><td>0.01</td><td>20 (3.8)</td><td>21 (4.0)</td><td>0.01</td></tr><tr><td>Head and neck</td><td>40 (7.5)</td><td>128 (6.1)</td><td>0.05</td><td>39 (7.5)</td><td>37 (7.1)</td><td>0.01</td></tr><tr><td>Urological and kidney</td><td>74 (13.9)</td><td>293 (13.9)</td><td>0.00</td><td>74 (14.2)</td><td>63 (12.1)</td><td>0.06</td></tr><tr><td>Gynecological</td><td>44 (8.3)</td><td>296 (14.1)</td><td>0.18</td><td>44 (8.5)</td><td>84 (16.2)</td><td>0.24</td></tr><tr><td>Endocrine surgery</td><td>5 (0.9)</td><td>24 (1.1)</td><td>0.02</td><td>5 (1.0)</td><td>3 (0.6)</td><td>0.04</td></tr><tr><td>Transplant</td><td>1 (0.2)</td><td>27 (1.3)</td><td>0.13</td><td>1 (0.2)</td><td>4 (0.8)</td><td>0.08</td></tr><tr><td>Plastic, cutaneous, breast</td><td>22 (4.1)</td><td>86 (4.1)</td><td>0.00</td><td>21 (4.0)</td><td>25 (4.8)</td><td>0.04</td></tr><tr><td>Orthopedic</td><td>46 (8.7)</td><td>200 (9.5)</td><td>0.03</td><td>42 (8.1)</td><td>46 (8.8)</td><td>0.03</td></tr><tr><td>Other</td><td>19 (3.6)</td><td>59 (2.8)</td><td>0.12</td><td>19 (3.7)</td><td>17 (3.3)</td><td>0.02</td></tr><tr><td>Surgical technique, n (%)</td><td></td><td></td><td>0.04</td><td></td><td></td><td>0.05</td></tr><tr><td>Open</td><td>405 (76.3)</td><td>1562 (74.3)</td><td></td><td>394 (75.8)</td><td>382 (73.5)</td><td></td></tr><tr><td>Minimally invasive</td><td>126 (23.7)</td><td>539 (25.7)</td><td></td><td>126 (24.2)</td><td>138 (26.5)</td><td></td></tr></tbody></table>

Abbreviations: BMI: Body Mass Index; ARISCAT: Assess Respiratory Risk in Surgical Patients in Catalonia; PPCs: Postoperative Pulmonary Complications; SpO2: Blood Oxygen Saturation; ASA: American Society of Anesthesiologists; COPD: Chronic Obstructive Pulmonary Disease; Obstructive Sleep Apnea Syndrome; GI: Gastrointestinal.

In contrast, a meta-analysis investigating preoperative smoking status and postoperative complications concluded that current smoking is associated with a nearly 2.5-fold increase in the risk of developing PPCs compared with non-smokers (RR =2.46, 95 % CI: 1.74–3.48) [1]. The difference in the outcome of PPCs compared to our study can be based on several factors. The meta-analysis was limited by a significant level of heterogeneity among the included studies focusing on pulmonary complications, due to inclusion of both cardiac and non-cardiac studies, variations in the follow up durations and different definitions of PPCs. Given the heterogeneity in the
definition of PPCs, the overall occurrence of PPCs among smokers varies greatly. Some studies only restrict to severe pulmonary complications including pneumonia or respiratory failure or acute respiratory stress syndrome [15–17], whereas others include more minor complications [18]. This possibly contributes to the wide range of reported PPC incidences in smokers, varying from 3.5 % to 37 %, making it difficult to compare outcomes between studies [19].

<table><caption>**Table 2**
Intraoperative characteristics unmatched and matched cohorts.</caption><thead><tr><th rowspan="2"></th><th colspan="3">Unmatched cohort</th><th colspan="3">Matched cohort</th></tr><tr><th>Smoker<br>N = 531</th><th>Non-smoker<br>N = 2101</th><th>SMD</th><th>Smoker<br>N = 520</th><th>Non-smoker<br>N = 520</th><th>SMD</th></tr></thead><tbody><tr><td>Tidal volume per PBW, ml·kg<sup>-1</sup>, median [IQR]</td><td>8.1 [7.2–9.1]</td><td>8.2 [7.4–9.2]</td><td>0.14</td><td>8.1 [7–9]</td><td>8.4 [7–9]</td><td>0.19</td></tr><tr><td>Peak pressure, cmH<sub>2</sub>O, median [IQR]</td><td>19 [16–22]</td><td>19 [16–22]</td><td>0.05</td><td>19 [16–22]</td><td>19 [16–22]</td><td>0.06</td></tr><tr><td>Plateau pressure, cmH<sub>2</sub>O, median [IQR]</td><td>17 [14–19]</td><td>17 [14–20]</td><td>0.11</td><td>17 [14–19]</td><td>17 [14–20]</td><td>0.09</td></tr><tr><td>PEEP, cmH<sub>2</sub>O, median [IQR]</td><td>5 [2–5]</td><td>5 [2–5]</td><td>0.01</td><td>5 [2–5]</td><td>4 [1–5]</td><td>0.01</td></tr><tr><td>Driving pressure, cmH<sub>2</sub>O, median [IQR]</td><td>12 [10–16]</td><td>13 [10–16]</td><td>0.13</td><td>12 [10–16]</td><td>12 [10–16]</td><td>0.08</td></tr><tr><td>Respiratory rate, breaths·min<sup>-1</sup>, median [IQR]</td><td>12 [12–13]</td><td>12 [12–13]</td><td>0.05</td><td>12 [12–13]</td><td>12 [12–13]</td><td>0.03</td></tr><tr><td>FiO<sub>2</sub>, %, median [IQR]</td><td>50 [43–60]</td><td>50 [45–60]</td><td>0.02</td><td>50 [43–60]</td><td>50 [44–60]</td><td>0.00</td></tr><tr><td>SpO<sub>2</sub>, %, median [IQR]</td><td>99 [98–100]</td><td>99 [98–100]</td><td>0.03</td><td>99 [98–100]</td><td>99 [98–100]</td><td>0.01</td></tr><tr><td>EtCO<sub>2</sub>, kPa, median [IQR]</td><td>34 [31–36]</td><td>33 [30–36]</td><td>0.05</td><td>34 [31–36]</td><td>34 [31–36]</td><td>0.02</td></tr><tr><td>Recruitment maneuvers, n (%)</td><td>74 (14.1)</td><td>263 (12.6)</td><td>0.04</td><td>73 (14.2)</td><td>73 (14.1)</td><td>0.00</td></tr><tr><td>Duration of surgery, min, median [IQR]</td><td>135 [70–201]</td><td>133 [79–200]</td><td>0.06</td><td>133 [70–200]</td><td>130 [78–192]</td><td>0.04</td></tr><tr><td>Duration of anaesthesia, min, median [IQR]</td><td>170 [105–245]</td><td>175 [110–250]</td><td>0.00</td><td>170 [105–245]</td><td>170 [110–235]</td><td>0.04</td></tr><tr><td>Epidural anaesthesia, n (%)</td><td>75 (14.1)</td><td>302 (14.4)</td><td>0.01</td><td>72 (13.8)</td><td>74 (14.2)</td><td>0.01</td></tr><tr><td>Neuromuscular blockade, n (%)</td><td>503 (95.1)</td><td>1978 (94.6)</td><td>0.02</td><td>492 (95.0)</td><td>491 (95.0)</td><td>0.00</td></tr><tr><td>Total fluids in, L, median [IQR]</td><td>1.7 [1.1–2.5]</td><td>1.8 [1.0–2.6]</td><td>0.02</td><td>1.8 [1.0–2.6]</td><td>1.8 [1.0–2.5]</td><td>0.03</td></tr><tr><td>Crystalloids, L</td><td>1.5 [1.0–2.2]</td><td>1.5 [1.0–2.2]</td><td>0.03</td><td>1.5 [1.0–2.1]</td><td>1.5 [1.0–2.1]</td><td>0.00</td></tr><tr><td>Colloids, L</td><td>0.5 [0.5–0.9]</td><td>0.5 [0.5–0.6]</td><td>0.07</td><td>0.5 [0.5–0.9]</td><td>0.5 [0.5–0.6]</td><td>0.05</td></tr><tr><td>Transfusion of packed red blood cells, n (%)</td><td>42 (7.9)</td><td>204 (9.7)</td><td>0.06</td><td>40 (7.7)</td><td>41 (7.9)</td><td>0.01</td></tr><tr><td>Units of red blood cell transfused, median [IQR]</td><td>2 [1–2]</td><td>2 [1–3]</td><td>0.08</td><td>2 [1–2]</td><td>2 [1–2]</td><td>0.01</td></tr></tbody></table>

Abbreviations: PBW: Predicted Body Weight; PEEP: Positive End-Expiratory Pressure; FiO<sub>2</sub>: Fraction of Inspired Oxygen; SpO<sub>2</sub>: Oxygen Saturation; EtCO<sub>2</sub>: End-tidal Carbon Dioxide.

<figure><img src="image_3.png" /><figcaption>**Fig. 2.** Distribution plot for postoperative pulmonary complications between smokers and non-smokers.</figcaption></figure>

Although the effect of smoking on overall PPCs remains unclear in patients at increased risk for PPCs, we found that smokers have a higher occurrence of respiratory failure compared to non-smokers. It is well-established that smoking impairs respiratory health through both acute exposure and chronic cumulative effects,
resulting in individuals being more susceptible to perioperative pulmonary complications [20]. Consequently, smoking remains an additional risk factor in the perioperative period [1,21]. Cessation of smoking prior to surgery is known to reduce the risk of PPCs, with a benefit that increases with the length of the cessation period before surgery [12]. Therefore, anaesthesiologists should emphasize that cessation of smoking is a critical intervention to reduce surgical risks and improve long-term health outcomes and should be actively pursued in the preoperative period [24]. [12].

<table><caption>**Table 3**
Outcomes according to smoking status in unmatched cohort.</caption><thead><tr><th rowspan="2"></th><th colspan="3">Unmatched cohort</th><th colspan="3">Matched cohort</th></tr><tr><th>Smoker<br>N = 531</th><th>Non-smoker<br>N = 2101</th><th>p-value</th><th>Smoker<br>N = 520</th><th>Non-smoker<br>N = 520</th><th>p-value</th></tr></thead><tbody><tr><td>Total PPC, n (%)</td><td>101 (19.0)</td><td>404 (19.2)</td><td>0.95</td><td>99 (19.0)</td><td>87 (16.7)</td><td>0.37</td></tr><tr><td>Mild PPC</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Unplanned supplementary oxygen</td><td>64 (12.1)</td><td>285 (13.6)</td><td>0.39</td><td>63 (12.1)</td><td>63 (12.1)</td><td>1.00</td></tr><tr><td>Severe PPCs</td><td>37 (7.0)</td><td>119 (5.7)</td><td>0.26</td><td>36 (6.9)</td><td>24 (4.6)</td><td>0.14</td></tr><tr><td>Respiratory failure</td><td>27 (5.1)</td><td>63 (3.0)</td><td>0.02</td><td>26 (5.0)</td><td>11 (2.1)</td><td>0.018</td></tr><tr><td>Need for invasive mechanical ventilation</td><td>9 (1.7)</td><td>52 (2.5)</td><td>0.34</td><td>9 (1.7)</td><td>11 (2.1)</td><td>0.82</td></tr><tr><td>ARDS</td><td>3 (0.6)</td><td>5 (0.2)</td><td>0.21</td><td>3 (0.6)</td><td>0 (0.0)</td><td>0.25</td></tr><tr><td>Pneumonia</td><td>6 (1.1)</td><td>22 (1.0)</td><td>0.82</td><td>5 (1.0)</td><td>5 (1.0)</td><td>1.00</td></tr><tr><td>Pneumothorax</td><td>1 (0.2)</td><td>3 (0.1)</td><td>1.00</td><td>0 (0.0)</td><td>1 (0.2)</td><td>1.00</td></tr><tr><td>Length of hospital stay, days, median [IQR]</td><td>4 [1-7]</td><td>4 [1-7]</td><td>0.79</td><td>4 [1-7]</td><td>4 [1-5]</td><td>0.82</td></tr><tr><td>In-hospital mortality, n (%)</td><td>4 (0.8)</td><td>36 (1.8)</td><td>0.16</td><td>4 (0.8)</td><td>4 (0.8)</td><td>1.00</td></tr></tbody></table>

Abbreviations: PPC: Postoperative Pulmonary Complication; ARDS: Acute Respiratory Distress Syndrome.

<figure><img src="image_4.png" /><figcaption>**Fig. 3.** LOVE-plot illustrating covariate balance between smokers and non-smokers before and after propensity score matching.</figcaption></figure>

For future studies, it is important to keep in mind that the incidence of PPCs in patients who use e-cigarettes has yet to be explored. Over recent years, the increase in e-cigarette usage has presented a potential risk factor for postoperative complications, given its association with acute lung injury and respiratory failure [22,23]. In LAS VEGAS, no data on e-cigarette use was collected. Therefore, further studies are needed to assess the impact of e-cigarette use on postoperative outcomes.

This study has several strengths. First, we used data from the LAS VEGAS study, a global prospective observational study in patients undergoing various types of surgery. The study had a multicentre design, conducted in both community and academic hospitals, thereby increasing the generalizability of the findings. The narrow 1-week timeframe of the study prevented temporal changes in intraoperative ventilation management, general care, and occurrence of PPCs. The robustness of LAS VEGAS was further supported by the minimal
amount of missing data and nearly complete follow-up of the outcome measures. We had an analysis plan in place before opening the database, which was strictly followed. We additionally performed propensity score matching to strengthen the reliability of our findings.

Our analysis has several limitations. First, this was a post hoc analysis of the observational LAS VEGAS study, which was not designed to assess the relationship between preoperative smoking status and post-operative outcomes. Although we adjusted for observed differences associated with PPCs through propensity score matching, we cannot rule out the possibility of yet unknown differences that may influence the findings. Second, LAS VEGAS originated from 2013. Since then, advancements in perioperative practices have been made, which could affect the applicability of our findings. Third, the preoperative smoking status was defined as smoker or non-smoker, with no further distinction between former smokers and never smokers. In addition, details on the number of pack years, lung function and timing of cessation were not recorded. Consequently, we cannot rule out that the non-smokers group may include individuals who ceased smoking shortly before undergoing surgery, potentially confounding the outcomes attributed to non-smokers. Last, our findings serve primarily as hypothesis-generating, as our findings regarding the relationship between smoking and PPCs can only imply associations rather than causation.

# 5. Conclusion

In this worldwide cohort of patients receiving intraoperative ventilation under general anaesthesia for surgery and at increased risk of PPCs, no difference was found in the occurrence of overall PPCs between smokers and non-smokers. However, compared to non-smokers, current smokers experienced a higher incidence of respiratory failure.

# Funding

LAS VEGAS was endorsed and partly funded by a research grant from the European Society of Anaesthesiology through their Clinical Trial Network. There was no additional funding for this analysis.

# CRediT authorship contribution statement

**Galina Dorland:** Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

**W. Saadat:** Writing – original draft, Formal analysis, Conceptualization.

**David M.P. van Meenen:** Writing – review & editing, Supervision, Project administration, Methodology, Formal analysis, Data curation, Conceptualization.

**Ary Serpa Neto:** Writing – review & editing, Project administration, Conceptualization.

**Michael Hiesmayr:** Writing – re-view & editing, Project administration, Conceptualization.

**Markus W. Hollmann:** Writing – review & editing, Supervision, Resources, Project administration, Methodology, Funding acquisition, Conceptualization.

**Gary H. Mills:** Writing – review & editing, Project administration, Conceptualization.
**Marcos F. Vidal Melo:** Writing – review & editing, Project administration, Conceptualization.

**Christian Putensen:** Writing – review & editing, Project administration, Conceptualization.

**Werner Schmid:** Writing – review & editing, Project administration, Conceptualization.

**Paolo Severgnini:** Writing – review & editing, Project administration, Conceptualization.

**Hermann Wrigge:** Writing – review & editing, Project administration, Conceptualization.

**Marcelo Gama de Abreu:** Writing – review & editing, Project administration, Conceptualization.

**Marcus J. Schultz:** Writing – original draft, Super-vision, Resources, Project administration, Methodology, Funding acquisition, Conceptualization.

**Sabrine N.T. Hemmes:** Writing – re-view & editing, Writing – original draft, Supervision, Project administration, Methodology, Formal analysis, Conceptualization.

**Michael Hiesmayr:** Writing – review & editing, Project administration, Conceptualization.

**Werner Schmid:** Writing – review & editing, Project administration, Conceptualization.

**David Kahn:** Writing – review & analysis, Data curation, Conceptualization.

**Marcel Gama de Abreu:** Writing – review & editing, Project administration, Conceptualization.

**Hermann Wrigge:** Writing – review & editing, Project administration, Conceptualization.

**Christian Nestler:** Writing – review & editing, Project administration, Conceptualization.

**Marco Baciarello:** Writing – review & editing, Project administration, Conceptualization.

**Paolo Severgnini:** Writing – review & editing, Project administration, Conceptualization.

**Sabrine Hemmes:** Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Formal analysis, Conceptualization.

**Marcus Schultz:** Writing – original draft, Supervision, Resources, Project administration, Methodology, Funding acquisition, Conceptualization.

**Markus Hollmann:** Writing – review & editing, Supervision, Resources, Project administration, Methodology, Funding acquisition, Conceptualization.

**Galina Gritsan:** Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

**Gary Minto:** Writing – review & editing, Project administration, Conceptualization.

**Gary Mills:** Writing – review & editing, Project administration, Conceptualization.

**Marcos Vidal Melo:** Writing – review & editing, Project administration, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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