EISA I. AFIFY, M.D.; AHMED T. SHAARAWY, M.D.; AHMED E. KABIL, M.D. and MAGDY S. TAHA, M.Sc.

Med. J. Cairo Univ., Vol. 84, o. 2, December: 377-383, 2016 www.medicaljournalofcairouniversity.net Comparison between Pressure Regulated Volume Control Ventilation and Synchronized Intermittent Mandatory Ventilation in Acute Exacerbations of Chronic Obstructive Pulmonary Disease EISA I. AFIFY, M.D.; AHMED T. SHAARAWY, M.D.; AHMED E. KABIL, M.D. and MAGDY S. TAHA, M.Sc. The Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Abstract Objective: The aim of this study was to to evaluate and compare the outcome of ventilation mode versus in the management of acute exacerbation of COPD requiring mechanical ventilation. Patients and Methods: The study included 70 consecutive patients presented with acute exacerbation of COPD who were indicated for invasive mechanical ventilation. Patients were randomly assigned into two groups, group I, which included 35 patients who were ventilated using mode, and group II, which included 35 patients who were ventilated using mode. All patients were subjected to thorough history taking, clinical examination, routine laboratory investigations, chest X-ray, ECG and blood gasses analysis. Ventilatory parameters after 24 hours of ventilation and outcomes were recorded in both groups. Results: After 24 hours of mechanical ventilation, Pa CO 2 was significantly improved in group I than in group II. There was improvement in O 2 saturation and Pa O 2 in group I compared to group II but without statistically significant difference. Peak Inspiratory Pressure (PIP) and Respiratory Rate (RR) were significantly lower in group I than in group II patients. Minute Ventilation (MV) was significantly higher in group I than group II patients. Unwanted/adverse outcomes and mortality were lower with mode than mode but without a statistically significant difference between both groups. Conclusions: mode appears to be superior to mode in ventilating COPD patients with acute exacerbations with a significantly lower peak inspiratory pressure and more effective ventilation. Key Words: Acute exacerbation of COPD Pressure regulated volume control ventilation () Synchronized intermittent mandatory ventilation (). Correspondence to: Dr. Ahmed E. Kabil, The Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Introduction MECHAICAL ventilation, either invasive or non-invasive, is a life saving measure in managing acute exacerbation of Chronic Obstructive Pulmonary Diseases (COPD). However mechanical ventilation can be associated with a significant morbidity and mortality. A good understanding of the underlying pathophysiologic mechanisms in acute exacerbation of COPD is very important in optimizing ventilatory strategies [1]. Volume control ventilation especially Synchronized Intermittent Mandatory Ventilation () has been a conventional mode of ventilation for decades, the main problem associated with volume control ventilation is the excessive airway pressure that can lead to barotrauma, volutrauma, and adverse hemodynamic effect, these problems can be minimized with pressure control ventilation, but one of the concerns with pressure-control ventilation is that it cannot guarantee a minimum minute ventilation in the face of changing lung mechanics or patient effort, or both, as pressure control modes generate a changeable tidal breath by delivering pressure over time [2]. In recent years, dual-control modes has been introduced in an attempt to combine the attributes of volume ventilation with the attributes of pressure ventilation to avoid both the high peak airway pressures of volume ventilation and also the varying tidal volume that may occur with pressure ventilation [3,4]. Pressure-Regulated Volume Control () mode, also known as adaptive pressure-controlled Continuous Mandatory Ventilation (CMV) or Volume Control plus (VC+), is a kind of dual-control 377

378 Comparison between & in Acute Exacerbations ventilation that uses tidal volume as a feedback control for continuously adjusting the pressure limit [5]. In, all breaths are mandatory, the rate is fixed, and the inspiratory pressure is varied to maintain a preset tidal volume [4]. Aim of the work: The main objective of this study was to evaluate the outcome of ventilation versus volume controlled ventilation in the management of acute exacerbation of COPD requiring mechanical ventilation. Patients and Methods The current prospective study was conducted at Respiratory Intensive Care Unit (RICU), Al- Hussein University Hospital over the period from ovember 2014 to June 2015. A written consent was taken from the first of kin of each patient, and the study was approved by the Ethical Committee of Medical Research of Al-Azhar University. The study included seventy consecutive patients who had acute exacerbation of COPD admitted to Respiratory Intensive Care Unit (RICU) and indicated for invasive mechanical ventilation for more than 24 hours. Inclusion criteria: Patients diagnosed as COPD on the basis of the clinical history, physical examination, and the findings of the chest radiograph, presence of acute exacerbation, with acute or acute on chronic respiratory failure, and the need for invasive mechanical ventilation more than 24 hour according to GOLD 2015 guidelines [6]. Exclusion criteria: COPD patients with one of the following conditions were excluded from the study: Acute respiratory distress syndrome. Acute myocardial infarction. Chronic renal failure. Decompensated liver cell failure. Massive pulmonary embolism. Pneumothorax. Massive pleural effusion. Also patients who were successfully extubated within the first 24h of ventilation were excluded. All the patients had undergone full history taking, (from the patients themselves or their first of kin), general and local examination, ABGs, routine lab investigations, radiology and electro- cardiogram. All patients were intubated and mechanically ventilated. Indications of mechanical ventilation included: Severe dyspnea and respiratory distress, respiratory frequency >35 breaths per minute, life-threatening hypoxemia (PaO 2 <40mmHg or PaO 2 /FiO 2 <200mmHg), severe acidosis (ph <7.25), hypercapnia (PaCO 2 >60mm- Hg), somnolence or impaired mental status and/or respiratory arrest. All patients received standard management lines for acute exacerbation of COPD according to GOLD 2015 guidelines [6]. All patients were ventilated using Heyer (i) TERIS adv. ventilator. (Heyer Medical AG, Germany). Sedation used was midazolam 0.1mg/kg in an interrupted daily boluses. The patients were randomly assigned into one of two groups: Group I: 35 patients were mechanically ventilated using mode. Group II: 35 patients were mechanically ventilated using mode. We compared between the two groups during this period in: Hemodynamics [pulse, Mean Arterial Pressure (MAP) which was calculated using the following formula: MAP=pdias + 1/3 (psys-pdias)]. Arterial blood gases. Ventilatory parameters: Peak Inspiratory Pressure (PIP), Respiratory Rate (RR), and Exhaled Minute Ventilation (ExhMV). For all the above measured s (MAP, RR, PIP, ExhMV) multiple readings at different intervals were recorded and only the mean of these readings was taken into statistical analysis. Also time to extubation, total ventilator days, ICU length of stay, ICU-free days and complications or adverse outcome in both study groups were compared. Study protocol: Patients were enrolled in the study when they fulfilled the inclusion criteria and were randomly assigned into one of the two groups either or groups, but all patients received all the standard treatment lines according to the GOLD 2015 [6]. Ventilator settings of both modes were tailored according to the clinical condition in each individual patient. Daily spontaneous-breathing trial was done for each patient, and weaning from mechanical ventilation was initiated as early as possible, once the patient fulfilled the following criteria for wean-

Eisa I. Afify, et al. 379 ing: PaO 2 >55mmHg; (SaO 2 >90) on FiO 2 of no more than 30-35, positive end expiratory pressure (PEEP) <5cm H2O, PH >7.35 with PaCO 2 <50 mmhg, hemodynamic stability as defined by the absence of hypotension and requiring no vasopressors, absence of abdominal paradox, afebrile, hemoglobin >9mg/dl, adequate mentation, the presence of adequate cough during suctioning, stable metabolic status (e.g., acceptable electrolytes, proteins) and resolution of acute phase of the disease. Weaning from mechanical ventilation was done using mode with pressure support for both groups and began to gradually reduce the preset RR as soon as the patient was capable of initiating a spontaneous breath; and when the patient's clinical status improved with FIO 2 <0.40, and set rate <10 breaths/min, patients were changed from to Pressure Support Ventilation (PSV) with a gradual decrease in the PSV levels to reach 8cm H2O as soon as they tolerated, and extubation was undertaken. Weaning failure was defined as the failure to pass a spontaneous-breathing trial after 1w of ventilation or the need for reintubation within 48h following extubation [7,8]. Results Table (1): Patients characteristics of in both study groups. Age in years: Mean ± SD 64.8±8.29 65.6±8.34 0.69 Gender: Male: 28 23 80.0 65.7 Female: 7 12 20.0 34.3 Smoking: Smoker: 5 4 14.3 11.4 Heavy smoker: 27 25 77.1 71.4 Biomass exposure: 3 6 8.6 17.1 0.282 0.349 Table (2): Prevalence of comorbidities in both study groups. DM: Hypertension: Heart disease: CKD: CLD: 13 37.1 12 34.3 11 31.4 2 5.7 2 5.7 DM : Diabetes Mellitus. CKD : Chronic Kidney Disease. CLD : Chronic Liver Disease. 12 34.3 8 22.9 8 22.9 3 8.6 1 2.9 1.000 0.427 0.591 1.000 1.000 Table (3): MAP, ABG and electrolyte analysis before ventilation in both study groups. MAP (mmhg) 90.29 5.18 90.43 4.11 0.899 FiO 2 28 28 1.000 PH 7.21 0.08 7.21 0.09 0.989 PaCO 2 (mmhg) 81.37 13.14 81.11 18.27 0.946 PaO 2 (mmhg) 48.57 9.01 49.11 6.31 0.771 SaO 2 () 79.49 12.27 79.06 11.91 0.883 K + (mmol/l) 4.35 0.314 4.26 0.702 0.760 a + (mmol/l) 136.40 7.93 138.57 6.35 0.210 HCO 3 (mmol/l) 30.49 8.26 30.14 9.23 0.870 Table (4): MAP, ABGs and electrolyte analysis after 24 hours of ventilation in both study groups. MAP (mmhg) 89.11 4.49 89.86 4.34 0.484 FiO 2 47 10.09 49.14 6.12 0.356 PH 7.34 0.07 7.36 0.06 0.151 PaCO 2 (mmhg) 55.54 8.12 50.31 10.15 0.020 PaO 2 (mmhg) 78.29 17.00 80.60 21.70 0.621 SaO 2 () 95.40 2.21 96.06 2.06 0.202 K + (mmol/l) 3.92 0.83 3.94 1.11 0.952 a + (mmol/l) 136.47 9.76 138.51 8.46 0.482 HCO 3 (mmol/l) 30.26 7.55 31.43 7.70 0.523

380 Comparison between PR VC & in Acute Exacerbations Table (4) showed that there was only a statistically significant difference as regard PaCO 2 (mm- Hg) after 24 hours of ventilation in both study groups. (p=0.020). Table (7) showed that there was no statistically significant difference as regard ICU length of stay, total ventilatory days and ICU free days in both study groups. Table (5): Ventilatory parameters during day 1 ventilation in both study groups. PIP (cmh 2 O) 24.97 2.59 19.31 1.67 0.0001 Total RR (bpm) 20.69 6.38 16.83 2.99 0.0019 MV (l/min) 8.03 2.15 10.09 1.98 0.0001 Table (5) showed that there was a statistically significant difference as regard ventilatory parameters during the first 24 hours of ventilation in PIP, spontaneous RR and exhaled MV in both study groups. p=0.0001, 0.0019, and 0.0001 respectively. Table (6): Rate of success/failure of extubation in both study groups. Successful extubation: Failed extubation: Odds ratio for successful extubation 95 CI z statistic 23 65.7 12 34.3 1.76 0.61 to 5.05 1.053 0.292 27 77.1 8 22.9 0.427 Table (6) showed that there was no statistically significant difference as regard rate of success/ failure of extubation in both study groups. Odds ratio for successful extubation 1.76 and p=0.292. Table (7): Total ventilator days, ICU length of stay, and ICUfree days in both study groups. Total ventilator days 3.6 2.90 3.34 1.23 0.6312 ICU LOS (days) 4.77 3.24 5.2 1.77 0.4957 ICU-free days 1.45 1.32 1.77 1.21 0.3111 Table (8): Incidence of unwanted/adverse outcomes in both study groups. Unwanted/adverse outcomes Failed extubation: 12 8 0.427 34.3 22.9 Shock: 8 6 0.765 22.9 17.1 VAP: 6 3 0.477 17.1 8.6 Stress ulcer: 2 1 1.000 5.7 2.9 Tracheostomy: 2 0 0.493 5.7 0.0 Pneumothorax: 2 1 1.000 5.7 2.9 Mortality: 6 4 0.733 17.1 11.4 Table (8) showed that as regard incidence of unwanted/adverse outcomes in both study groups it was lower in group but there was no statistically significant difference. Mortality in group was 6 (17.1) and in group was 4 (11.4), 0.733. Table (9): Showed that was no statistically significant difference as regard outcome (survival and mortality) in both study group (p=0.734), but there was statistically significant difference as regard outcome in each group separately ( p<0.001).

Eisa I. Afify, et al. 381 Table (9): Comparison between groups as regard outcome. Groups Chi-square test Total number χ 2 Survival 35 (100) 31 (88.57) 35 (100) 29 (82.86) 0.116 0.734 (S) Outcome Mortality 4 (11.4) 6 (17.1) χ 2 38.657 27.697 Chi-square test <0.001 (HS) <0.001 (HS) Discussion Mechanical ventilation, either invasive or noninvasive, is a life saving measure in managing acute respiratory failure due to acute exacerbation of COPD. However mechanical ventilation can be associated with a significant morbidity and mortality. A good understanding of the underlying pathophysiologic mechanisms in acute exacerbation of COPD is very important in optimizing ventilatory strategies [9]. In recent years, dual-control modes has been introduced in an attempt to combine the attributes of volume ventilation with the attributes of pressure ventilation, to avoid both the high peak airway pressures of volume ventilation and also the varying tidal volume that may occur with pressure ventilation. Pressure-Regulated Volume Control () mode is a kind of dual-control ventilation that uses tidal volume as a feedback control for continuously adjusting the pressure limit which may achieve the goals of patient-ventilator synchrony, effective respiratory system support, adequate gas exchange, and limited ventilator-induced lung injury [3]. The present study was designed to evaluate and compare ventilation versus in the management of acute exacerbation of COPD requiring mechanical ventilation. Two groups were included into this study. Group I, included 35 patients with acute exacerbation of COPD, admitted to the intensive care unit and subjected to invasive mechanical ventilation using mode, and group II, included 35 patients with acute exacerbation of COPD, admitted to the intensive care unit and subjected to invasive mechanical ventilation using mode. There was no statistically significant difference between the two groups as regard age, gender, smoking habits, comorbidities, Mean Arterial Blood Pressure (MAP), ABGs and electrolytes before initiation of mechanical ventilation. But there was a statistically significant decrease in PaCO 2 (50.31 ± 10.15) level in the ABG in group than (55.54±8.13) group during the period of ventilation. Also as regard ventilatory parameters [total RR, exhmv and PIP] after 24 hour of ventilation in both study groups, total RR was lower in the (16.83 ±2.99) group than (20.69 ±6.39) group, and the exhaled MV (exhmv) (l/ min), was higher in (10.09± 1.98) group than (8.03 ±2.15) group with a statistically significant difference as regard these two parameters. Also the PIP was lower in the (19.31 ± 1.68) group than the (24.97±2.59) group with a statistically significant difference. All these findings may be explained by volume assurance which is obtained during all breaths in mode, while in mode, volume assurance occurs only in mandatory and assisted breaths not the spontaneous breaths, leading to more work of breathing in mode than, and giving the the advantage of better alveolar ventilation with CO 2 clearance and lower PIP than mode. Rate of successful extubations was better in group than group, 77.1 (n=27/35) vs. 65.7 (n=23/35), but there was no statistically significant difference. Also total ventilator days and ICU-free days were less in group, with no statistically significant difference. On the other hand as regard ICU LOS (days), it was longer in the group than the group (5.2 ± 1.78 days) vs. (4.77 ±3.25 days) but also without a statistically significant difference. As regard incidence of unwanted/adverse outcomes (failed extubation, irreversible shock, VAP, stress ulcer, tracheostomy, pneumothorax and mortality) it was lower in mode but there was no statistically significant difference between both groups and this may be due to small number of patients in this study. These results are in agreement with Kesecioglu et al., 1996 who compared VCV and (using an inverse inspiratory-expiratory ratio) with a pig model of saline-lavage-induced acute respiratory distress syndrome, and reported that had

382 Comparison between & in Acute Exacerbations lower airway pressures and slightly better gas exchange than VCV with a constant inspiratory flow [11]. It is also in agreement with Alvarez et al., who compared, VCV, and pressure-limited, timecycled ventilation, with 10 adult patients suffering from acute respiratory failure. And found that had lower peak airway pressures and slightly better carbon dioxide clearance as well [12]. This is also in agreement with Abou Shehata et al., who evaluated the outcome of ventilation in the management of ARF of different pulmonary diseases. They studied 79 patients with Acute Respiratory Failure (ARF) of different pulmonary disorders who required mechanical ventilation, 32 (40.5) of whom had COPD with acute on top of chronic respiratory failure. They concluded that ventilation improves oxygenation parameters in ARF of different etiologies and is equally effective in management of ARF of different pulmonary disorders [13]. Also, these results are in agreement with Chang et al., who compared and in elderly patients with acute exacerbations of COPD and respiratory failure. They found that application of resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure and concluded that can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation-volume control [14]. Conclusion: This study shows the advantage of using the mode for ventilation during acute respiratory failure due to acute exacerbation of COPD. PIP was lower for all patients using the mode compared to the mode, and alveolar ventilation was better as indicated by the decline in PaCO2. References 1- REDDY R.M. and GUTUPALLI K.: Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease. International Journal of COPD, 2 (4): 441-5, 2007. 2- CABODEVILA E.M., GUZMA E.D., HERESI G.A. and CHATBUR R.L.: Alternative modes of mechanical ventilation: A review for the hospitalist. Cleveland Clinic J. of Med., 76 (7): 417-30, 2009. 3- BRASO R.D. AD CHATBUR R.L.: Should adaptive pressure control modes be utilized for virtually all patients receiving mechanical ventilation? Respir Care, 52 (4): 478-88, 2007. 4- PIERSO D.J.: Invasive mechanical ventilation, in: R.K. Albert, S.G. Spiro, J.R. Jett (Eds.), Clinical Respiratory Medicine, second ed., Philadelphia Saunders, London, pp. 189-209, 2004. 5- SOH J.W., KOH Y., LIM C.M., LEE J.D., SHIM T.S., DO LEE S., KIM W.S., KIM D.S. and KIM W.D.: The usefulness of Pressure-Regulated Volume Control () mode in mechanically ventilated patients with unstable respiratory mechanics, Tuber. Respir. Dis., 44 (6): 1318, 1997. 6- GOLD: The global initiative for chronic obstructive lung disease, Caught from <http://www.goldcopd.org >, 2015. 7- CORRADO A., GIAI R., VILLELLA G., GORII M., AUGUSTYE R., TOZZI A., PERIS A., GRIFOI S., MESSORI A., OZZOLI C. and BERI G.: Iron lung versus conventional mechanical ventilationin acute exacerbation of COPD, Eur. Respir. J., 23: 419-24, 2004. 8- BOLES J.M., BIO J., COORS A., et al.: Weaning from mechanical ventilation, Eur. Respir. J., 29: 1033-56, 2007. 9- REDDY R.M. and GUTUPALLI K.: Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease. International Journal of COPD, 2 (4): 441-5, 2007. 10- TIRUVOIPATI R., BAGASH M., MAKTELOW B., et al.: Decelerating flow ventilation effects in acute respiratory failure, J. Crit. Care, 23 (1): 101-10, 2008. 11- SACHDEV K., CHUGH D., GUPTA, et al.: Comparison of two ventilation modes and their clinical implications in sick children, Indian J. Crit. Care Med., 9: 205-10, 2005. 12- ALVAREZ A., SUBIRAA M. and BEITO S.: Decelerating flow ventilation effects in acute respiratory failure, J. Crit. Care, 13 (1): 21-5, 1998. 13- ABOUSHEHATA M.E., AMIA M. ABD EL- MAKSOUD and R.A. ELMETWALLY: Pressureregulated volume controlled ventilation in acute respiratory failure of pulmonary diseases. Egyptian Journal of Chest Diseases and Tuberculosis, 61: 151-8, 2012. 14- CHAG S., SHI J., FU C., WU X. and LI S.: A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure. Int. J. Chron. Obstruct. Pulmon. Dis., 11: 1023-9, 2016.

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