NOVEMBER/DECEMBER 2022 VOL 33 NO 6 • Short-term prognosis af ter thoracoscopic lobectomy • Inf lammatory parameters and postoperat ive del i r ium • Verapami l and pressure over load- induced ventr icular arrhythmias • Prosthet ic vascular graf t management in above-knee amputat ions • Gender and systemic immune–inf lammat ion index wi th new-onset hypertension • Ant icoagulat ion in pregnant women wi th mechanical prosthet ic heart valves • Subacute dual stent thromboses in a COVID-19-posi t ive pat ient CardioVascular Journal of Afr ica (off icial journal for PASCAR) www.cvja.co.za
ISSN 1995-1892 (print) ISSN 1680-0745 (online) Cardiovascular Journal of Afr ica www.cvja.co.za CONTENTS INDEXED AT SCISEARCH (SCI), PUBMED, PUBMED CENTRAL AND SABINET Vol 33, No 6, NOVEMBER/DECEMBER 2022 EDITORS Editor-in-Chief (South Africa) PROF PAT COMMERFORD Assistant Editor PROF JAMES KER (JUN) Regional Editor DR A DZUDIE Regional Editor (Kenya) DR F BUKACHI Regional Editor (South Africa) PROF R DELPORT EDITORIAL BOARD PROF PA BRINK Experimental & Laboratory Cardiology PROF R DELPORT Chemical Pathology PROF MR ESSOP Haemodynamics, Heart Failure & Valvular Heart Disease DR OB FAMILONI Clinical Cardiology DR V GRIGOROV Invasive Cardiology & Heart Failure PROF J KER (SEN) Hypertension, Cardiomyopathy, Cardiovascular Physiology DR J LAWRENSON Paediatric Heart Disease PROF A LOCHNER Biochemistry/Laboratory Science DR MT MPE Cardiomyopathy PROF DP NAIDOO Echocardiography PROF B RAYNER Hypertension/Society PROF MM SATHEKGE Nuclear Medicine/Society PROF YK SEEDAT Diabetes & Hypertension PROF H DU T THERON Invasive Cardiology INTERNATIONAL ADVISORY BOARD PROF DAVID CELEMAJER Australia (Clinical Cardiology) PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology) DR GEORGE A MENSAH USA (General Cardiology) PROF WILLIAM NELSON USA (Electrocardiology) DR ULRICH VON OPPEL Wales (Cardiovascular Surgery) PROF PETER SCHWARTZ Italy (Dysrhythmias) PROF ERNST VON SCHWARZ USA (Interventional Cardiology) SUBJECT EDITORS Nuclear Medicine and Imaging DR MM SATHEKGE Heart Failure DR G VISAGIE Paediatric DR S BROWN Paediatric Surgery DR DARSHAN REDDY Renal Hypertension DR BRIAN RAYNER Surgical DR F AZIZ Adult Surgery DR J ROSSOUW Epidemiology and Preventionist DR AP KENGNE Pregnancy-associated Heart Disease PROF K SLIWA-HAHNLE EDITORIAL 289 ‘Between a rock and a couple of hard places’ BJ Cupido CARDIOVASCULAR TOPICS 291 Effects of intra-operative fluid management under the guidance of stroke volume variability on short-term prognosis after thoracoscopic lobectomy F Zhu • S Cheng • Y Yang • X Li • Z Tang 296 The role of inflammatory parameters in the prediction of postoperative delirium in patients undergoing coronary artery bypass grafting H Şaşkin • KS Özcan • S Yildirim 304 Influence of verapamil on pressure overload-induced ventricular arrhythmias by regulating gene-expression profiles X Cheng • X Xu • C Zou • W Jiang 313 Prosthetic vascular graft management in above-knee amputations L Umur • I Selçuk 317 The relationship between gender and systemic immune–inflammation index in patients with new-onset essential hypertension E Altuntas • U Cetın • S Usalp
CONTENTS Vol 33, No 6, NOVEMBER/DECEMBER 2022 FINANCIAL & PRODUCTION CO-ORDINATOR ELSABÉ BURMEISTER Tel: 021 976 8129 Fax: 086 664 4202 Cell: 082 775 6808 e-mail: elsabe@clinicscardive.com PRODUCTION EDITOR SHAUNA GERMISHUIZEN Tel: 021 785 7178 Cell: 083 460 8535 e-mail: shauna@clinicscardive.com CONTENT MANAGER MICHAEL MEADON (Design Connection) Tel: 021 976 8129 Fax: 0866 557 149 e-mail: michael@clinicscardive.com The Cardiovascular Journal of Africa, incorporating the Cardiovascular Journal of South Africa, is published 10 times a year, the publication date being the third week of the designated month. COPYRIGHT: Clinics Cardive Publishing (Pty) Ltd. LAYOUT: Jeanine Fourie – TextWrap PRINTER: Tandym Print/Castle Graphics ONLINE PUBLISHING & CODING SERVICES: Design Connection & Active-XML.com All submissions to CVJA are to be made online via www.cvja.co.za Electronic submission by means of an e-mail attachment may be considered under exceptional circumstances. Postal address: PO Box 1013, Durbanville, RSA, 7551 Tel: 021 976 8129 Fax: 0866 644 202 Int.: +27 21 976 8129 e-mail: info@clinicscardive.com Electronic abstracts available on Pubmed Audited circulation Full text articles available on: www.cvja. co.za or via www.sabinet.co.za; for access codes contact elsabe@clinicscardive.com Subscription: To subscribe to the online PDF version of the journal, e-mail elsabe@clinicscardive.com • R500 per issue (excl VAT) • R2 500 for 1-year subscription (excl VAT) The views and opinions expressed in the articles and reviews published are those of the authors and do not necessarily reflect those of the editors of the Journal or its sponsors. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by the relevant control authorities. REVIEW ARTICLE 322 A clinical conundrum: review of anticoagulation in pregnant women with mechanical prosthetic heart valves M Jenneker • H Ramnarain • H Sebitloane CASE REPORT 329 Subacute dual stent thromboses in a COVID-19-positive patient J Liebenberg • T-J John • H Khalfey • I D’Andrea • C Kyriakakis PASCAR SEMINAR 333 PASCAR Clinical Research Training Task Force seminar CARDIO NEWS 334 First for Africa: robotic-assisted cardiothoracic surgery comes to South Africa PUBLISHED ONLINE (Available on www.cvja.co.za and in PubMed)
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 AFRICA 289 ‘Between a rock and a couple of hard places’ Blanche J Cupido DOI: 10.5830/CVJA-2023-001 The management of the pregnant patient with a mechanical prosthetic valve remains a challenging clinical problem, even with recent advances in valve technology, diagnostic and therapeutic strategies. The WHO classification for the assessment of pregnancy risk gives it a class III, which is a significant risk to mother and foetus. The recent ROPAC registry data showed an event-free pregnancy with a resultant live birth in 58% of women with mechanical valves compared to 78% in women with cardiac disease and no valve intervention.1 The morbidity and mortality rates for both mother and foetus relate largely to complications stemming from the use of anticoagulation and bleeding, and thromboembolic events. Jenneker et al. (page 322) provides a comprehensive overview of the current literature and some of the recommendations put forward by the two major international guideline bodies, the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC). They go on to make a recommendation/algorithm for assessment that is used in their local setting, Inkosi Albert Sisulu Central Hospital, in Durban, KwaZulu-Natal. Rightfully, the importance of pre-conception counselling and planning is highlighted, together with the proposal of shared decision-making, consisting of a robust and honest discussion of risks and benefits of each regimen with the prospective mother. The three most frequently used strategies are (note, all strategies, swop over to a heparin-based regimen at 36/37 weeks of gestation): • Warfarin throughout all three trimesters: this regimen is only really to be considered if the required dose of warfarin is to remain within the therapeutic international normalised ratio (INR) range of < 5 mg per day. This is the one considered to have the lowest rate of maternal thrombotic complications, but with a higher rate of foetal miscarriage. The foetal complications are dose dependent (AHA /ACC2 class IIa B/ ESC3 class IIa C recommendation). • Low-molecular-weight heparin (LMWH) or intravenous (IV) unfractionated heparin (UFH) in the first trimester with switching to warfarin in the second and third trimesters (AHA/ACC2 class IIa B/ESC3 class IIa C). • LMWH or UFH throughout all three trimesters: although this regimen poses the lowest risk to the foetus, the rate of maternal thrombotic complications can be as high as 33% (AHA/ACC2 class IIb B/ESC3 class IIb C). Unless there is a particularly valid reason with a high risk of warfarin complications, this option is not ideal. The data supporting these recommendations are from observational studies andmeta-analyses, all of which are wrought with problems of heterogeneity, making direct comparisons between different treatment regimens extremely difficult. The recommendations are therefore frequently noted as level of evidence C (expert opinion or consensus based).2,3 When deciding on a particular strategy, the following considerations are to be taken into account in determining the risk–benefit ratio to both the mother and foetus. Some of these challenges are particularly amplified in the South African context and include: • Adequate anticoagulation with vitamin K antagonists (VKA) (warfarin) and time in therapeutic range (TTR). Numerous local observational studies have noted the difficulty in maintaining TTR in South Africa. A recent retrospective, observational study conducted at two large INR clinics in the Western Cape showed that the mean TTR was 47%, with a mere 25.1% of patients achieving good INR control.4 Given the increased thrombotic risk in pregnancy, it is imperative to have facilities available for effective testing and more frequent INR testing compared to the non-pregnant state. • Staffing, bed availability and IV access. The strategy of IV UFH poses a number of challenges. Patient admission and IV access for a number of weeks is required. The risks of infection from drip sites and the added burden of continued intensive clinical care (doctor and nursing care) in resourcepoor environments make this a less attractive option. • The availability of factor X levels timeously and regularly is a prerequisite to LMWH use. Both the AHA/ACC2 and the ESC3 give the use of LMWH without regular factor Xa monitoring a class III recommendation, which means it could constitute harm. During pregnancy, the faster renal clearance may result in lower levels. There is no true consensus on the frequency of monitoring levels. The ESC recommends weekly levels whereas the ACC/AHA makes no time recommendation. A big concern remains that although the use of LMWH has gained widespread popularity in our clinical environment, with a favourable risk-factor profile, there is a distinct paucity of availability and resources for factor Xa level monitoring. • What is a definite ‘NO’? It is important to note that there is no place for the use of aspirin on its own. The addition of aspirin to VKA, although acceptable by the AHA/ACC (class IIb), is not recommended by the ESC, who raise the concern of limited data supporting benefit but with an increased risk of bleeding complications. Given the difficulty of access to emergency care in South Africa, this is to be used with extreme caution. Editorial Department of Cardiology, University of Cape Town, Cape Town, South Africa Blanche J Cupido, MB ChB, FCP (SA), Cert Cardio (SA), MPhil (UCT), FACC, FESC, blanche.cupido@uct.ac.za
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 290 AFRICA The use of a direct-acting oral anticoagulants for anticoagulation of mechanical prosthetic valves is contra-indicated. A landmark phase 2 study of dabigatran versus warfarin in 252 patients with mechanical prosthetic mitral or aortic valves was stopped early due to excess thromboembolic and bleeding complications in the dabigatran arm. For this reason, novel oral anticoagulants are not recommended as an alternative to warfarin in mechanical prosthetic valves.5 The clinical decision-making in the pregnant patient with a mechanical prosthetic valve remains challenging. Each case is to be considered on an individual level, with consultation and buy-in from both the patient and clinician in a suitably resourced environment. References 1. Van Hagen IM, Roos-Hesselink JW, Ruys TP, Merz WM, Goland S, Gabriel H, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation 2015; 132: 132–142. 2. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143(5): e35–e71. 3. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. The TaskForce for theManagement of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Endorsed by: the International Society of Gender Medicine (IGM), the German Institute of Gender in Medicine (DGesGM), the European Society of Anaesthesiology (ESA), and the European Society of Gynecology (ESG). Eur Heart J 2018; 39: 3165–3241. 4. Ebrahim I, Bryer A, Cohen K, Mouton JP, Msemburi W, Blockman M. Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa. S Afr Med J 2018; 108(6): 490–494. 5. Eikelboom JW, Connolly S, Breuckmann M, Granger C, Kappetein A, Mack M, et al. for the RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Eng J Med 2013; 369: 1206–1214. Systemic corticosteroids a potential treatment for heart failure: Spanish study Intravenous corticosteroids did not hurt people with acute heart failure (HF), and could be a potential treatment for those with more inflammation, according to a hypothesisgenerating study based on Spain’s Epidemiology of Acute Heart Failure in the Emergency Departments (EAHFE) registry. Whereas acuteHFpatients receiving corticosteroid therapy in the emergency department (ED) saw no improvement in all-cause mortality at 30 days, there was a trend of more favourable point estimates for survival in those with elevated C-reactive protein (CRP) levels. Medpage Today reports that potential for an association between corticosteroid therapy and better outcomes was observed among people with the most inflammation, defined as CRP > 40 mg/l – findings that were nevertheless statistically non-significant based on the available data: • All-cause mortality at 30 days: 11.8% with corticosteroids vs 19.4% without (HR 0.56, 95% CI 0.20–1.55) • Post-discharge ED revisit at 30 days: 42.3 vs 43.8% (HR 0.92, 95% CI 0.52–1.62) • In-hospital all-cause mortality: 8.8 vs 13.4% (HR 0.61, 95% CI 0.17–2.14). ‘The present analysis suggests that corticosteroids might have the potential to improve outcomes in acute HF patients with inflammatory activation,’ wrote study authors Dr Gad Cotter of Momentum Research in Chapel Hill, North Carolina, and colleagues in ESC Heart Failure. Inflammation has been linked to HF, though antiinflammatory therapies have failed in chronic HF, the researchers said, citing the failures of infliximab and etanercept in the older ATTACH and RENEWAL studies, respectively. ‘Although corticosteroids have been classically viewed as anti-inflammatory agents, they can cause sodium and water retention, potentially leading to worsening of HF. However, it has been reported that the administration of corticosteroids to patients with severe acute HF produced a potent diuretic effect and improved fluid overload and renal function,’ said the investigators. ‘Added to previous studies of potentially improved diuresis, the [present] results suggest that future randomised trials on anti-inflammatory therapy are needed to assess potential benefit in patients with the highest degree of inflammation,’ Cotter and co-authors said. EAHFE was a registry that included 45 Spanish EDs from 2007 to 2018. For the present analysis, the investigators included 1 109 people (median age of 81.2 years, 45% of whom were men) with NT-proBNP > 300 pg/ml and CRP > 5 mg/l in the ED. The team excluded people taking chronic systemic corticosteroids and those who had had acute HF triggered by an infection. Of the study cohort, 10.9% of patients received at least one IV bolus corticosteroid treatment. This group tended to have higher systolic blood pressure, lower room air oxygen saturation, and were more likely to have cerebrovascular disease, peripheral artery disease, chronic obstructive pulmonary disease and dementia. Their index acute HF episode was more commonly triggered by hypertensive crisis, compared with non-corticosteroid users. The retrospective study was limited by the potential for confounding, a relatively small sample of corticosteroid users, and a lack of details regarding dose and duration of treatment in the database, Cotter and colleagues acknowledged. Source: MedicalBrief 2022
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 AFRICA 291 Cardiovascular Topics Effects of intra-operative fluid management under the guidance of stroke volume variability on short-term prognosis after thoracoscopic lobectomy Feng Zhu, Shaolin Cheng, Yang Yang, Xuan Li, Zhen Tang Abstract Aim: We aimed to explore the influence of intra-operative fluid management under the guidance of stroke volume variability (SVV) on the short-term prognosis after thoracoscopic lobectomy. Methods: A total of 171 eligible patients from April 2017 to April 2019 were selected. All patients received intra-operative fluid management under the guidance of SVV, and were divided into low-, middle- and high-level groups (n = 57) using a random-numbers table. The general data, respiratory function indices at different time points, haemodynamic indices at different time points, use of vasoactive drugs, shortterm prognosis indices and incidence of complications were compared. Results: There were no significant differences in age, gender, operation time, one-lung ventilation time, amount of bleeding, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, lung compliance and peak airway pressure at different time points, usage amount of anisodamine and incidence rate of complications among the three groups. In the low-level group, the fluid infusion amount and urine volume were significantly larger, the forced expiratory volume in one second (FEV1), percentage of FEV1 in the predicted value (FEV1%pred) and FEV1/forced vital capacity (FEV1/FVC) seven days after operation were higher, and the six-minute walk test (6MWT) distance was longer than those in the other two groups. The usage amount of dopamine, norepinephrine and esmolol was smaller, and the postoperative exhaust time was shorter than those in the other two groups. The low-level group had a smaller usage amount of isosorbide dinitrate injection and shorter length of postoperative hospital stay than the high-level group. Stroke volume had a significant difference at T2 and T3 in the low-level group, central venous pressure (CVP) and stroke volume had significant differences at T2 and T3 in the middle-level group, and heart rate (HR), mean arterial pressure and CVP were significantly different at T2 and T3 in the high-level group. Conclusion: Fluid management under the guidance of lowlevel SVV (8% ≤ SVV ≤ 9%) was conducive to the maintenance of stable haemodynamics in patients during thoracoscopic lobectomy, thereby improving short-term prognosis. Keywords: stroke volume variability, fluid management, thoracoscopic lobectomy, short-term prognosis, complication Submitted 14/5/21, accepted 9/10/21 Published online 27/10/22 Cardiovasc J Afr 2022; 291–295 www.cvja.co.za DOI: 10.5830/CVJA-2021-049 Lung cancer is a commonmalignant tumour with a high incidence rate, accounting for 13% of all cancers.1 The mortality rate of patients with lung cancer also tops the list among malignancies, seriously threatening the life of patients.2 Histologically, lung cancer is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the latter of which is dominant, accounting for 85% of the total.3 Therapeutic regimens are different for patients with different subtypes of lung cancer. For example, SCLC patients are mainly treated with chemoradiotherapy, while surgical resection is mainly adopted for early- and mid-stage NSCLC patients, in which lobectomy is an effective treatment means of NSCLC.4 Traditional open lobectomy is associated with great trauma, which may lead to postoperative complications and cause damage to the patient’s body, seriously affecting the prognosis of patients.5 In contrast, thoracoscopic lobectomy is associated with less trauma, milder postoperative pain, faster recovery and fewer postoperative complications.6 With a good visual field during the operation, thoracoscopic lobectomy can completely remove the lesions and reduce unnecessary damage to the blood vessels and lung tissues.7 As a commonly used non-physiological ventilation strategy in thoracic surgery, one-lung ventilation can reduce intraoperative mechanical damage and postoperative infection, but it may result in volume overload and pulmonary oedema.8 Intra-operative fluid management under the guidance of stroke volume variability (SVV), through dynamically monitoring Department of Cardiothoracic Surgery, Bengbu First People’s Hospital, Bengbu, China Feng Zhu, MD Shaolin Cheng, MD Yang Yang, MD Xuan Li, MD Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China Zhen Tang, MD, atnitinodebt@web.de, yifangang935@163.com
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 292 AFRICA haemodynamic parameters, can reflect the volume status in the body in real time, lower the incidence rate of postoperative complications and ameliorate the prognosis of patients.9 In our study, the influence of intra-operative fluid management under the guidance of SVV on the short-term prognosis after thoracoscopic lobectomy was explored. Methods This study was approved by the hospital’s ethics committee, and written informed consent was obtained from all patients. A total of 171 patients undergoing thoracoscopic lobectomy for lung cancer in our hospital from April 2017 to April 2019 was selected as the research subjects. All patients received intra-operative fluid management under the guidance of SVV, and they were divided into a low-level group (n = 57, 8% ≤ SVV ≤ 9%), a middle-level group (n = 57, 10% ≤ SVV ≤ 11%) and a high-level group (n = 57, 12% ≤ SVV ≤ 13%) using a random-numbers table. In the low-level group, there were 37 males and 20 females aged 50–75 years, with an average age of 63.42 ± 6.08 years. In the middle-level group, there were 32 males and 25 females aged 51–75 years, with an average of 61.73 ± 5.82 years. In the high-level group, there were 28 males and 29 females aged 52–73 years, with an average age of 62.41 ± 5.73 years. Inclusion criteria were as follows: (1) patients meeting the diagnostic criteria for NSCLC,10 and diagnosed with NSCLC through imaging or pathological examination, (2) those with surgical indications for lobectomy, (3) those in the American Society of Anesthesiologists (ASA) class I–II, (4) those without other respiratory diseases except lung cancer, and (5) those with complete clinical data. Exclusion criteria were as follows: (1) patients complicated with immune system diseases, (2) those with a history of severe infection one week before admission, (3) those complicated with underlying diseases such as hypertension or diabetes, (4) those with mental illness, (5) those accompanied by tumours in other systems or blood diseases, or (6) those with poor compliance. The general data of patients were collected using the electronic medical record, including age, gender, operation time and one-lung ventilation time, fluid infusion amount, amount of bleeding and urine volume during the operation. T1 was defined as the time of stable breathing and haemodynamics during two-lung ventilation after double-lumen tube tracheal intubation. T2 was the time of stable breathing and haemodynamics after two-lung ventilation was replaced with one-lung ventilation, with the patient’s position changed from the horizontal to a lateral position, and T3 was the time of stable breathing and haemodynamics after one-lung ventilation was replaced with two-lung ventilation, with the patient’s position changed from the lateral position to a horizontal position. At T1, T2 and T3, the arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), lung compliance (LC) and peak airway pressure (PAP) were recorded. At T1, T2 and T3, the heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) and stroke volume (SV) were recorded. The usage amount of vasoactive drugs anisodamine (654-2), dopamine, norepinephrine, esmolol and isosorbide dinitrate injection (ABEL) during the operation was recorded. Short-term prognosis indices: the pulmonary function of patients was determined seven days after the operation, including forced expiratory volume in one second (FEV1), percentage of FEV1 in the predicted value (FEV1%pred), forced vital capacity (FVC) and the six-minute walk test (6MWT) distance, based on which FEV1/FVC was calculated. In addition, the postoperative exhaust time, stitch removal time and length of postoperative hospital stay were recorded. Statistical analysis SPSS 19.0 software was used for statistical analysis. Numerical data are expressed as percentage, and intergroup comparison was made by chi-squared test. Measurement data are expressed as mean ± standard deviation, intergroup comparison was conducted by the independent t-test, and intragroup comparison by the paired t-test. Repeated-measures analysis of variance was performed at different time points among the groups, and the independent-samples t-test was adopted at each time point among groups. A p-value < 0.05 was considered statistically significant. Results The fluid infusion amount and urine volume were significantly smaller in the high-level group compared to those in the other two groups (p < 0.05). There were no significant differences in other general data between the three groups (p > 0.05) (Table 1). There were no significant differences in respiratory functions PaO2, PaCO2, LC and PAP at different time points in the three groups (p > 0.05) (Table 2). SV had a significant difference at T2 and T3 in the low-level group (p < 0.05), CVP and SV had significant differences at T2 and T3 in the middle-level group (p < 0.05), and the differences in HR, MAP and CVP were significant at T2 and T3 in the highlevel group (p < 0.05) (Table 3). In the low-level group, the amount of vasoactive drugs dopamine, norepinephrine and esmolol used was significantly less than that in the other two groups, and the amount of ABEL used was also significantly less than that in the high-level group (p < 0.05). No significant difference was found in the amount of 654-2 used in the three groups (p > 0.05) (Table 4). Short-term prognosis indices FEV1, FEV1%pred, FEV1/FVC and 6MWT distance showed no significant differences among the three groups before the operation (p > 0.05), while they Table 1. General data General data Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) Age (years) 63.42 ± 6.08 61.73 ± 5.82 62.41 ± 5.73 Male/female (n) 37/20 32/25 28/29 Operation time (hours) 4.70 ± 0.67 4.83 ± 0.62 4.93 ± 0.58 One-lung ventilation time (hours) 3.52 ± 0.49 3.72 ± 0.53 3.47 ± 0.50 Fluid infusion amount (ml) 2906.73 ± 302.41 2710.31 ± 263.46* 2503.42 ± 245.37*# Amount of bleeding (ml) 146.42 ± 48.31 144.85 ± 46.65 142.78 ± 47.52 Urine volume (ml) 1698.74 ± 285.42 1583.46 ± 264.36* 1425.78 ± 252.64*# *p < 0.05 vs low-level group; #p < 0.05 vs middle-level group.
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 AFRICA 293 all had significantly increased seven days after the operation compared with those before operation (p < 0.05). In the low-level group, postoperative FEV1, FEV1%pred and FEV1/FVC were significantly higher, and 6MWT distance was significantly longer than those in the other two groups, while the postoperative exhaust time was significantly shorter than that in the other two groups. In addition, the low-level group had significantly shorter length of postoperative hospital stay than the high-level group (p < 0.05). There was no significant difference in the stitch removal time in the three groups (p > 0.05) (Table 5). Postoperative complications occurred in a small number of patients, including pulmonary oedema, pulmonary infection, hypertension, arrhythmia and pulmonary embolism. The incidence rate of postoperative complications was not significantly different between the low-level (3.51%), middle-level (8.77%) and high-level groups (10.53%) (p > 0.05) (Table 6). Discussion Lung cancer, a common malignancy, has a high incidence rate. Its mortality rate is the highest among male patients worldwide and among female patients in developed countries.11 Lung cancer is caused by many factors, mainly including occupational toxic exposure, tobacco, genetic factors, chronic respiratory diseases and environmental pollution.12 Histologically, lung cancer can be classified into SCLC and NSCLC, which are mainly treated with chemoradiotherapy and lobectomy, respectively.13 With the development of minimally invasive surgical techniques, these have been widely applied in the surgical treatment of a variety of diseases. Compared with traditional open lobectomy, thoracoscopic lobectomy can completely remove the lesions and possesses such advantages as milder postoperative pain, less trauma, faster postoperative Table 2. Respiratory function at different time points Variables Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) PaO2 (100 mmHg) T1 402.48 ± 90.35 405.64 ± 88.26 398.73 ± 85.42 T2 202.18 ± 80.42 198.64 ± 79.85 195.73 ± 76.65 T3 358.65 ± 98.31 361.18 ± 100.49 365.72 ± 102.44 PaCO2 (100 mmHg) T1 40.64 ± 3.12 41.26 ± 2.85 40.35 ± 2.73 T2 39.18 ± 2.92 40.87 ± 2.94 40.78 ± 3.05 T3 39.34 ± 2.61 41.65 ± 3.22 38.96 ± 2.49 LC (l/cm H2O) T1 39.12 ± 7.05 38.47 ± 6.85 37.96 ± 6.24 T2 26.08 ± 5.12 25.83 ± 4.87 26.54 ± 5.23 T3 35.42 ± 5.73 36.18 ± 6.05 36.43 ± 5.85 PAP (100 mmHg) T1 15.96 ± 2.42 16.03 ± 2.58 15.37 ± 2.18 T2 23.15 ± 3.41 22.85 ± 3.07 22.67 ± 2.83 T3 17.85 ± 3.28 17.69 ± 3.31 17.26 ± 2.99 PaO2: arterial partial pressure of oxygen; PaCO2: arterial partial pressure of carbon dioxide; LC: lung compliance; PAP: peak airway pressure; T1: time of stable breathing and haemodynamics during two-lung ventilation after doublelumen tube tracheal intubation; T2: time of stable breathing and haemodynamics after two-lung ventilation is replaced with one-lung ventilation; T3: time of stable breathing and haemodynamics after one-lung ventilation is replaced with two-lung ventilation. Table 3. Haemodynamics at different time points Variables Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) HR (beats/min) T2 70.68 ± 6.52 71.15 ± 6.28 72.31 ± 7.02 T3 72.41 ± 6.94 75.65 ± 7.92 79.28 ± 8.43* MAP (mmHg) T2 94.72 ± 9.21 95.31 ± 8.94 97.36 ± 9.64 T3 98.31 ± 8.42 97.64 ± 9.28 87.42 ± 8.85* CVP (mmHg) T2 7.85 ± 1.47 7.43 ± 1.29 7.12 ± 1.31 T3 6.65 ± 1.34 5.12 ± 1.25* 5.64 ± 1.06* SV (ml) T2 69.92 ± 9.74 70.22 ± 10.18 71.37 ± 10.85 T3 82.96 ± 9.46* 78.87 ± 8.25* 76.31 ± 8.75 HR: heart rate; MAP: mean arterial pressure; CVP: central venous pressure; SV: stroke volume; T2: time of stable breathing and haemodynamics after two-lung ventilation is replaced with one-lung ventilation; T3: time of stable breathing and haemodynamics after one-lung ventilation is replaced with two-lung ventilation. *p < 0.05 vs T2. Table 4. Use of vasoactive drugs in the three groups Vasoactive drugs Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) Anisodamine (mg) 0.32 ± 0.17 0.35 ± 0.18 0.29 ± 0.14 Dopamine (mg) 26.12 ± 12.31 33.98 ± 12.47* 48.72 ± 13.42*# Norepinephrine (μg) 27.85 ± 14.37 42.06 ± 20.18* 52.05 ± 23.16*# Esmolol (mg) 7.85 ± 3.74 9.62 ± 4.06* 12.13 ± 5.28*# Isosorbide dinitrate (mg) 6.59 ± 2.31 7.22 ± 2.42 8.13 ± 3.12* *p < 0.05 vs low-level group; #p < 0.05 vs middle-level group. Table 5. Short-term prognosis indices Variables Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) FEV1 (l) Before operation 1.48 ± 0.35 1.46 ± 0.32 1.50 ± 0.31 7 days after operation 2.35 ± 0.82# 1.96 ± 0.73*# 1.75 ± 0.68*#§ FEV1%pred (%) Before operation 34.65 ± 6.83 33.96 ± 5.41 33.69 ± 5.52 7 days after operation 40.85 ± 6.18# 38.51 ± 5.83*# 36.15 ± 5.62*#§ FEV1/FVC (%) Before operation 52.18 ± 8.15 52.24 ± 8.25 52.79 ± 8.31 7 days after operation 69.47 ± 8.75# 62.42 ± 8.22*# 58.41 ± 7.88*#§ 6MWT distance (m) Before operation 263.74 ± 30.18 262.65 ± 31.40 260.73 ± 30.25 7 days after operation 306.72 ± 41.25# 280.17 ± 38.16*# 265.14 ± 40.38*#§ Postoperative exhaust time (hours) 83.16 ± 20.15 91.37 ± 22.74* Stitch removal time (days) 12.31 ± 3.14 12.65 ± 2.87 Length of postoperative hospital stay (days) 15.26 ± 4.84 16.58 ± 5.12 FEV1: forced expiratory volume in one second; FEV1%pred: percentage of FEV1 in the predicted value; FEV1/FVC: forced expiratory volume in one second/ forced vital capacity; 6MWT: six-minute walk time. *p < 0.05 vs low-level group; #p < 0.05 vs middle-level group; §p < 0.05 vs before operation. Table 6. Incidence of complications in the three groups Complications Low-level group (n = 57) Middle-level group (n = 57) High-level group (n = 57) Pulmonary oedema 0 0 1 Pulmonary infection 0 1 0 Hypertension 1 2 3 Arrhythmia 1 1 1 Pulmonary embolism 0 1 1 Total, n (%) 2 (3.51) 5 (8.77) 6 (10.53)
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 294 AFRICA recovery and fewer postoperative complications, greatly reducing the damage to the body of patients.14 One-lung ventilation, as a non-physiological ventilation strategy, is usually required during lobectomy. This method isolates the two lungs, reduces the incidence rate of postoperative infection, and alleviates mechanical damage and lung injury during operation.15 However, one-lung ventilation can easily lead to rapid fluctuations in haemodynamics, leading to hypoxia– reperfusion injury in patients, inducing lung inflammation, acute respiratory distress syndrome and acute lung injury, with a mortality rate of 25–60%, seriously affecting surgical effect and the prognosis of patients.16 Moreover, the volume overload caused by one-lung ventilation will also affect the organ’s functional recovery, causing postoperative complications.17 Reasonable fluid management can offer satisfactory tissue perfusion and oxygen supply and keep the haemodynamics stable in patients during lobectomy. SVV, a new guidance for fluid management, can be used to accurately predict the volume status of patients during operation, so that the cardiac preload is optimised, the effective circulating blood volume is maintained, and arterial oxygenation is improved, thus reducing the incidence of postoperative complications and ameliorating the prognosis.18 However, fluid management under the guidance of different levels of SVV has varying effects on the intra-operative and postoperative indices, surgical effect and postoperative complications in patients undergoing thoracoscopic lobectomy. Therefore, it is particularly important to optimise the SVV level for guiding the fluid management during lobectomy, enhancing the treatment effect on patients, and improving the prognosis of patients. Respiratory failure is a common complication in patients with lung cancer during and after lobectomy, which can cause death in severe cases, do great harm to the health of patients, and affect the surgical efficacy.19 Therefore, respiratory function indices PaO2, PaCO2, LC and PAP should be monitored in real time during lobectomy for lung cancer patients. As for the important indices for haemodynamic changes, HR, MAP, CVP and SV, Benes et al.20 compared the influence of goal-orientated fluid therapy under the guidance of SVV and traditional fluid therapy on the haemodynamic parameters of elderly patients undergoing radical surgery of lung cancer at different time points. They found that the cardiac index, MAP and CVP had the most obvious changes in the traditional fluid therapy group at different time points, while goal-orientated fluid therapy under the guidance of SVV could stabilise the peri-operative haemodynamics in patients. In our study, the haemodynamics was relatively stable in the low-level group, consistent with the literature report. Lung damage is usually found in lung cancer patients after lobectomy. FEV1, FEV1%pred, FVC, FEV1/FVC and 6MWT are all important indices for assessing the lung function, and they can also be used to evaluate the postoperative short-term prognosis of patients. In addition, postoperative exhaust time, stitch removal time and postoperative length of hospital stay are also key indices used to assess the postoperative short-term prognosis of patients. In the present study, in the low-level group, postoperative FEV1, FEV1%pred and FEV1/FVC were significantly higher, and 6MWT distance was significantly longer than those in the other two groups, while the postoperative exhaust time was significantly shorter than that in the other two groups. Besides, the low-level group had significantly shorter length of postoperative hospital stay than the high-level group. Complications such as pulmonary oedema, pulmonary infection, hypertension, arrhythmia and pulmonary embolism often occur in lung cancer patients after lobectomy. According to a study, fluid management under the guidance of SVV is able to markedly reduce the incidence of complications after thoracoscopic lobectomy.21 In this study, the incidence rate of postoperative complications was not significantly different among the three groups. This study has limitations. It was a single-centre study with a small sample size. The findings herein will be further validated by our group by performing multi-centre studies with larger sample sizes. Conclusion Fluid management under the guidance of low-level SVV (8% ≤ SVV ≤ 9%) was conducive to the maintenance of stable haemodynamics in patients during thoracoscopic lobectomy, thereby improving the short-term prognosis of patients. References 1. Shen J, Wang B, Zhang T, et al. Suppression of non-small cell lung cancer growth and metastasis by a novel small molecular activator of RECK. Cell Physiol Biochem 2018; 45(5): 1807–1817. 2. Domblides C, Antoine M, Hamard C, et al. Nonsmall cell lung cancer from HIV-infected patients expressed programmed cell death-ligand 1 with marked inflammatory infiltrates. AIDS 2018; 32(4): 461–468. 3. Zhang X, Wu L, Xu Y, et al. Trends in the incidence rate of lung cancer by histological type and gender in Sichuan, China, 1995–2015: A singlecenter retrospective study: LC incidence rate trends in Sichuan. Thorac Cancer 2018; 9(5): 532–541. 4. Zou Y, Sun Y, Guo B, et al. α3β1 Integrin-targeting polymersomal docetaxel as an advanced nanotherapeutics for non-small cell lung cancer treatment. ACS Appl Mater Interfaces 2020; 12(13): 14905– 14913. 5. Alghamdi ZM, Lynhiavu L, Moon YK, et al. Comparison of nonintubated versus intubated video-assisted thoracoscopic lobectomy for lung cancer. J Thorac Dis 2018; 10(7): 4236–4243. 6. Zhang R, Kyriss T, Dippon J, et al. Impact of comorbidity burden on morbidity following thoracoscopic lobectomy: A propensity-matched analysis. J Thorac Dis 2018; 10(3): 1806–1814. 7. Richardson MT, Backhus LM, Berry MF, et al. Intraoperative costs of video-assisted thoracoscopic lobectomy can be dramatically reduced without compromising outcomes. J Thorac Cardiovasc Surg 2018; 155(3): 1267–1277. 8. Sheybani S, Sharifian Attar A, Golshan S, et al. Effect of propofol and isoflurane on gas exchange parameters following one-lung ventilation in thoracic surgery: a double-blinded randomized controlled clinical trial. Electron Physician 2018; 10(2): 6346–6353. 9. Al-Ghamdi AA. Intraoperative fluid management: Past and future, where is the evidence? Saudi J Anaesth 2018; 12(2): 311–317. 10. Funkhouser Jr WK, Hayes DN, Moore DT, et al. Interpathologist diagnostic agreement for Non–Small cell lung carcinomas using current and recent classifications. Arch Pathol Lab Med 2018; 142(12): 1537–1548. 11. Yao D, Gu P, Wang Y, et al. Inhibiting polo-like kinase 1 enhances radiosensitization via modulating DNA repair proteins in non-small-cell
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 AFRICA 295 lung cancer. Biochem Cell Biol 2018; 96(3): 317–325. 12. Meyers DE, Bryan PM, Banerji S, et al. Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer. Curr Oncol 2018; 25(4): e324–e334. 13. Zhou B, Wang D, Sun G, et al. Effect of miR-21 on apoptosis in lung cancer cell through inhibiting the PI3K/Akt/NF-κB signaling pathway in vitro and in vivo. Cell Physiol Biochem 2018; 46(3): 999–1008. 14. Bongiolatti S, Gonfiotti A, Vokrri E, et al. Thoracoscopic lobectomy for non-small-cell lung cancer in patients with impaired pulmonary function: analysis from a national database. Interact Cardiovasc Thorac Surg 2020; 30(6): 803–811. 15. Long Y, Zeng Q, He X, et al. One-lung ventilation for percutaneous thermal ablation of liver tumors in the hepatic dome. Int J Hypertherm 2020; 37(1): 49–54. 16. Lema Tome M, De la Gala FA, Piñeiro P, et al. Behavior of stroke volume variation in hemodynamic stable patients during thoracic surgery with one-lung ventilation periods. Rev Bras Anestesiol 2018; 68(3): 225–230. 17. Chan W H, Huang T W, Cheng C P, et al. Predict fluid responsiveness by stroke volume variation in patients undergoing protective one-lung ventilation in pressure-controlled ventilation mode. J Med Sci 2019; 39(3): 135–139. 18. Lee YH, Jang HW, Park CH, et al. Changes in plasma volume before and after major abdominal surgery following stroke volume variationguided fluid therapy: a randomized controlled trial. Minerva Anesthesiol 2019; 86(5): 507–517. 19. Bolourani S, Wang P, Patel V M, et al. Predicting respiratory failure after pulmonary lobectomy using machine learning techniques. Surgery 2020; 168(4): 743–752. 20. Benes J, Giglio M, Brienza N, et al. The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials. Crit Care 2014; 18(5): 584. 21. Sahutoglu C, Turksal E, Kocabas S, et al. Influence of stroke volume variation on fluid treatment and postoperative complications in thoracic surgery. Ther Clin Risk Manag 2018; 14: 575–581.
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 296 AFRICA The role of inflammatory parameters in the prediction of postoperative delirium in patients undergoing coronary artery bypass grafting Hüseyin Şaşkin, Kazim Serhan Özcan, Serhan Yildirim Abstract Objective: In this study, we aimed to evaluate the association of pre-operative and early postoperative inflammatory parameters with postoperative delirium in patients operated on for coronary artery bypass grafting. Methods: The data of 1 279 cardiac surgery patients operated on between June 2014 and March 2020 were analysed retrospectively. Among these, 777 (61.2%) patients operated on for isolated coronary artery bypass grafting surgery with cardiopulmonary bypass were enrolled. Two groups were formed. The patients who developed postoperative delirium were placed in group 1 (n = 187) and the patients with uneventful postoperative follow up (n = 590) were enrolled in group 2. Results: Pre- and early postoperative mean platelet volume, C-reactive protein level, erythrocyte sedimentation rate, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were elevated in group 1 (p = 0.0001). The APACHE II score and duration of hospital and intensive care unit stay were significantly elevated in group 1 (p < 0.05). An early-stage neurological event was observed in eight patients (4.3%) in group 1 and 12 patients (2%) in group 2, which was not statistically significantly different between the groups (p = 0.09). In-hospital mortality was observed in three patients (1.6%) in group 1 and five patients (0.8%) in group 2, which did not show a statistically significant difference (p > 0.05). In univariate and multivariate regression analysis, the pre-operative platelet-to-lymphocyte ratio (p = 0.013), mean platelet volume (p = 0.0001) and erythrocyte sedimentation rate (p = 0.002) were determined as independent risk factors for the occurrence of delirium in the early postoperative period. Also, the postoperative platelet-to-lymphocyte ratio (p = 0.0001), neutrophil-to-lymphocyte ratio (p = 0.0001) and erythrocyte sedimentation rate (p = 0.0001) were determined as independent risk factors for the occurrence of delirium in the early postoperative period. Conclusion: Pre- and early postoperative inflammatory parameters were observed to be predictors of postoperative delirium in patients operated on for coronary artery bypass grafting. Keywords: coronary artery bypass grafting surgery, delirium, inflammation Submitted 16/5/21, accepted 7/2/22 Published online 4/3/22 Cardiovasc J Afr 2022; 296–303 www.cvja.co.za DOI: 10.5830/CVJA-2022-008 Coronary artery bypass grafting (CABG) is a life-saving procedure with acceptable complication and mortality rates.1 Most of the mortality and morbidity events associated with cardiac surgery are related to cerebrovascular complications.2,3 Brain injury associated with CABG may present as a pure neurological complication or a neuropsychological dysfunction.2 Postoperative delirium (POD) is reported in 26 to 52% of patients undergoing cardiac surgery and is associated with increased length of intensive care unit (ICU) stay, morbidity, mortality and cognitive decline.4-6 Although several risk factors have been defined, the exact underlying pathophysiology of POD has not been clearly elucidated. Neuro-inflammation is considered to be one of the possible contributors for POD.7 Surgical trauma initiates an inflammatory response, which promotes healing; however, when this response is dysregulated, it can result in a neuro-inflammatory response, leading to postoperative cognitive decline.8 The cascade of events starts with generalised inflammation, leading to endothelial dysfunction, which increases the permeability of the blood–brain barrier and leads to the development of inflammatory changes of the nervous tissue, damage to neurons and exaggerated responses of microglial cells.9 Research involving biomarkers for diagnosis and prognosis did not indicate any single marker for delirium screening, but rather a panel of biomarkers were identified that may lead to an accurate and timely diagnosis of delirium.10 A complete blood count (CBC) is a routine test performed on almost every patient in daily practice. The information provided by a CBC is greater than what is commonly thought and its use cannot be overestimated.9 Inflammation leads to a transient increase in white blood cells (WBC) and a decrease in platelets. Recently, neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) were identified as prognostic markers in various cardiovascular and cerebrovascular diseases.11-13 Egberts et al. observed that increased NLR was a predictor of delirium in elderly patients admitted to a geriatric unit.14 Recently, Kotfis Cardiovascular Surgery Clinic, Derince Training and Research Hospital, Health Sciences University, Kocaeli, Turkey Hüseyin Şaşkın, MD, sueda_hs@yahoo.com Department of Cardiology, Siyami Ersek Training and Research Hospital, Health Sciences University, İstanbul, Turkey Kazim Serhan Özcan, MD Neurology Clinic, Derince Training and Research Hospital, Health Sciences University, Kocaeli, Turkey Serhan Yildirim, MD
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 AFRICA 297 et al. observed that PLR and platelet-to-WBC ratio (PWR) were predictors of delirium after cardiac surgery.9 The aim of this study was to evaluate the association of inflammatory markers derived from CBC, mean platelet volume (MPV), PLR, NLR, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with POD in patients operated on for CABG. Methods In this study, the medical records of 1 269 patients who were operated on for isolated CABG with cardiopulmonary bypass (CPB) for coronary artery disease by the same surgical team in the Cardiovascular Surgery Clinic of the University of Health Sciences, Kocaeli Derince Training and Research Hospital between June 2014 and December 2020 were investigated retrospectively. The patients with signs of POD were evaluated using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scores and through the use of anti-psychotics such as dexmedetomidine hydrochloride or haloperidol.15 The exclusion criteria were pre-operative dementia, history of a psychiatric disorder such as depression or cognitive disorder, history of opioid use or drug abuse, advanced age (> 75 years), acute or chronic renal failure, history of head injury, peripheral artery disease, valvular disease, additional procedures such as carotid artery or congenital heart surgery with CABG, chronic obstructive pulmonary disease, left ventricular systolic function disorder (left ventricular ejection fraction < 40%), congestive heart failure, history of myocardial infarction within the previous month, haematological proliferative disease, low haemoglobin levels (≤ 10 g/dl), patients who were severely overweight (body mass index > 30 kg/m2), pre-operative atrial and ventricular arrhythmia, cerebrovascular accident within the last six months prior to surgery, neoplastic disease including benign and malignant tumours, endocrinological disorders (hypothyroidism, hyperthyroidism), autoimmune diseases, systemic inflammatory diseases, the use of steroids or non-steroidal anti-inflammatory drugs, immunosuppressive drug treatment within the final two weeks prior to surgery, the presence of clinical infection signs (fever 37.5°C, CRP ≥ 5 mg/dl, ESR > 20 mm/h or leukocyte count > 11 000 cells/µl) before surgery, application of femoral artery cannulation due to calcification of the ascending aorta, emergency surgery, CABG surgery on a beating heart, patients who were re-operated due to haemodynamic instability or bleeding, patients who required intra-aortic balloon pump, prolonged intubation (> 24 hours) and re-operations. In our clinic, examinations of the anastomosis sites of the aorta are performed by palpation, as we do not perform computed tomography pre-operatively on a regular basis. In patients who were ineligible for side clamping, proximal anastomoses were performed under a single cross-clamping period. These patients were also excluded from our study. A total of 777 patients (597 males, 180 females; mean age 59.8 ± 8.4 years, range 30–75 years) who did not receive any psychiatric treatment in the pre-operative period, who had normal carotid and vertebral artery systems with Doppler ultrasonography and who were operated on for isolated elective CABG were included in the study. The patients were divided into two groups. Group 1 (n = 187) consisted of patients with manifestations of delirium developed within the first 72 hours of surgery, while group 2 (n = 590) included patients with uneventful postoperative follow up. All data were accessed using the archives and the recorded database of the hospital. The demographic and clinical characteristics of the patients, CBC routinely studied pre-operatively and postoperatively (leukocytes, platelets, lymphocytes, neutrophils, MPV, haematocrit and haemoglobin), as well as creatinine, ESR and CRP levels were recorded. Data, including the number of distal anastomoses, the use of blood products and inotropic support, duration of aortic cross-clamp, CPB time, intubation duration and length of stay in the ICU and in hospital were analysed. In addition, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores for all patients were recorded. Arterial hypertension was considered in patients with measurements of blood pressure above 140 mmHg systolic and 90 mmHg diastolic on at least three occasions or active use of antihypertensive medication. Diabetes mellitus was defined as fasting plasma glucose levels above 126 mg/dl (6.99 mmol/l) in at least two different measurements or active use of antidiabetic drugs. Smoking was defined as current smoking or ex-smokers who quitted smoking in the last six months. Hyperlipidaemia was accepted as total cholesterol > 220 mg/dl (5.7 mmol/l) and low-density lipoprotein cholesterol > 130 mg/dl (3.37 mmol/l) or use of antihyperlipidaemic drugs. Cerebrovascular accident was accepted as acutely developed, temporary or permanent new major (type II) focal or global deficit occurring within the first 24 hours and not lasting for 72 hours postoperatively.16 All patients with a diagnosis of cerebrovascular accident were assessed by the neurologist and the diagnoses were confirmed through imaging studies. Approximately 5 to 7ml venous blood samples were placed into a sterile tube with EDTA for routine blood analysis. Haematological parameters were calculated by an automated blood count device (Abbott CELL-DYN 3700; Abbott Laboratory, Abbott Park, Illinois, USA) following a waiting time of one hour. PLR was calculated by dividing the number of thrombocytes by the number of lymphocytes. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Postoperative stroke was accepted as a new focal neurological deficit for a period longer than 24 hours, for which the new ischaemic brain damage was shown with computed tomography or magnetic resonance imaging. The diagnosis of postoperative atrial fibrillation (AF) was made by standard 12-derivation electrocardiography. Morbidity and mortality during the stay in hospital following the operation or during the first 30 postoperative days were accepted as postoperative early-term morbidity and mortality. Prolonged stay in the hospital was defined as seven days or longer. This study complied with the Declaration of Helsinki and was carried out following approval of the Ethics Committee for Clinical Trials of Kocaeli Derince Training and Research Hospital of the University of Health Sciences. All patients received 0.5 mg oral alprazolam anaesthesia on the night before surgery. Intramuscular 5 mg midazolam was injected 30 minutes before the operation as pre-medication. Intravenous midazolam (0.1 mg/kg), fentanyl (0.01 mg/kg) and rocuronium bromide (0.6 mg/kg) were administered for induction. Intravenous rocuronium bromide (0.15 mg/kg) and midazolam (0.03 mg/kg) were given for maintenance.
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