CLINICAL PRESENTATION AND PREDICTORS OF OUTCOME IN PATIENTS WITH SEVERE ACUTE EXACERBATION OF COPD REQUIRING ADMISSION TO ICU By Mohan et al

BACKGROUND COPD is a common, costly preventable disease and is the 4 th leading cause of death globally Acute exacerbation of COPD(AE-COPD) is a common cause of ER visit Major cause of morbidity and mortality with more than half of these patients requiring re-admission in subsequent 6 months Great variability in clinical course making predictions of outcome in a given patient difficult The study was designed to prospectively study the clinical presentation and predictors of outcome in patients with AE-COPD requiring admission to ICU

METHODS During period from June 2000 and December 2004, 914 patients diagnosed with COPD in MOPD and Chest Clinic at a Tertiary Hospital 314 of these later on presented to ER with AE-COPD After appropriate initial treatment, 116 admitted to Medical ICU, 18 discharged, 180 admitted to Acute Medical Unit and Medical Ward Basis of study is on the 116 admitted to ICU Patients with bronchiectasis, interstitial lung disease,PE, Pulmonary Oedema excluded Study was approved by Ethical Committee

COPD diagnosed on basis of Pulmonary Function tests during MOPD visits AE-COPD diagnosed if all following present: rapid worsening dyspnoea, increase in sputum volume and purulence Only single enrolement per patient regardless of frequency of exacerbations On arrival full Hx including type of smoking habit cigarette or bidi and pack years, domestic fuel use and examination Baseline investigations including imaging

O2 given as appropriate nasal prongs, face mask or Ventura devices Nebs of Salbutamol/Ipratropium every 15 min to 8 hourly, steroids if no improvement iv aminophylline. Empiric antibiotics given could be changed on sensitivities No standard criterion for Invasive Ventilation In study indications include, failure to respond to pharmacologic and other non-ventilatory Rx, severe dyspnoea, severe acidosis (pH 60mmHg), life threating hypoxaemia, respiratory arrest, somnolence, impaired mental status and co-morbid illness

STATISTICAL ANALYSIS Variables following normal distribution were summarised by mean and standard deviation Association between two categorical variables was by χ2 or Fisher’s exact test as appropriate Student t test used for quantitative variables Quantitative variables categorised and if it showed statistically significant association with outcome at p < 0.20 considered for inclusion Stepwise multivariate logistic regression performed with potential candidate variables as co-variates SYSTAT Version 7.0 used. All stat tests performed were two tailed, p <0.05 considered statistically significant

RESULTS. Mean age 62.1 ± 9.8 years with 102(88%) males.Mean duration of COPD 7.2 ± 5.8 years.All males were smokers for 22.3 ± 11.2 pack years 35.2% smoked cigarettes and 64.8 % smoked bidis. All women non-smokers and were exposed to domestic fuels.81 (69.8%) patients had co-morbid illness with 53 (45.7%) having one condition and 28(54.3%) having 2 or more.Past PTB in 33(28.4%) patients, 5 patients with Type 2 DM found to have active PTB.ABG showed Respiratory Failure in 40(33.8 %) patients Type 1 in 17.5% and Type 2 in 82.5%.Invasive Ventilation required in 18 patients.16 (13.7%) patients died in the study Predictors of death: need for invasive ventilation, presence of co-morbid illness and hypercapnoea

Table 1 Demographic characteristics and co-morbid conditions in 116 patients with acute exacerbation of chronic obstructive pulmonary disease admitted to the medical intensive care unit Age (years) (mean ± SD)62.1 ± 9.8 Gender Male102 Female14 Smoking (all males)22.3 ± 11.2 pack years Duration of symptoms (years) (mean ± SD)7.6 ± 5.2 COPD, GOLD stage* Moderate [No. (%)]25 (21.6) Severe [No. (%)]55 (47.4) Very severe [No. (%)]36 (31.0) Co-morbid conditions Hypertension [No. (%)]40 (34.5) Alcoholism [No. (%)]38 (32.8) Type II diabetes mellitus [No. (%)]36 (31.0) † Past pulmonary tuberculosis [No. (%)]33 (28.4) ‡ Coronary artery disease [No. (%)]12 (10.3) Chronic renal failure [No. (%)]10 (08.6) Number of co-morbid illnesses 0 [No. (%)]35 (30.2) 1 [No. (%)]53 (45.7) 2 [No. (%)]18 (15.5) 3 [No. (%)]07 (06.0) 4 [No. (%)]03 (02.6) GOLD = Global Initiative for Chronic Obstructive Lung Disease (reference 1) COPD = chronic obstructive pulmonary disease * In all patients post-bronchodilator forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) was ≤ 0.7. Moderately severe COPD, FEV 1 = 50 – 80% predicted; severe COPD, FEV 1 = 30 – 50% predicted; very severe COPD = <30% predicted (reference 1) † 3 patients had diabetic ketoacidosis and 5 patients had active pulmonary tuberculosis ‡ Clinical and radiographic evidence of past tuberculosis was present More than one co-morbid conditions were present in several patients Mohan et al. BMC Pulmonary Medicine :27 doi: /

Table 2 Clinical presentation in 116 patients with acute exacerbation of chronic obstructive pulmonary disease admitted to the medical intensive care unit JVP = jugular venous pulse Mohan et al. BMC Pulmonary Medicine :27 doi: / Variable% Symptoms Cough100 Increased sputum volume100 Increased sputum purulence100 Recent rapid worsening of dyspnea100 Accessory muscle use60.3 Inability to complete a full sentence while talking60.3 Pedal edema19.8 Fever29.3 Altered sensorium12.9 Upper respiratory infection8.6 Gastroesophageal reflux7.8 Signs Wheezing100 Respiratory rate > 24/min94 Crepitations56 Cyanosis33.6 Heart rate > 100/min25 Elevated JVP12.9 Systolic BP < 90 mm Hg3.4

Table 3 Laboratory abnormalities in 116 patients with acute exacerbation of chronic obstructive pulmonary disease admitted to the medical intensive care unit ESR = erythrocyte sedimentation rate Mohan et al. BMC Pulmonary Medicine :27 doi: / Variable% Polycythemia (PCV >54% in men, >49% in women)32.8 Leukocytosis [(>12 × 103/mm3), (>12 × 109/l)]64.7 Neutrophilia [(> 70%), (> 0.7)]77.6 Elevated ESR (>20 mm at the end of the first hour)64.7 Hypoalbuminemia [(< 3.5 g/dl), (< 35 g/dl)]19.0 Hyponatremia [serum sodium < 120 meq/l, (< 120 mmol/l)]16.4 Hypokalemia [serum potassium < 3.5 meq/l, (< 3.5 mmol/l)]16.4 Hyperbilirubinemia [(>1.2 mg/dl), (> 20.5 μmol/l)]6.0 Elevated transaminases [>50 IU/l]22.4 Elevated blood urea [(>50 mg/dl), (>17.9 mmol/l)]45.7 Elevated serum creatinine [(>1.5 mg/dl), (> μmol/l)]19.0

Table 4 Predictors of outcome in 116 patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to the intensive care unit: univariate sensitivity analysis Mohan et al. BMC Pulmonary Medicine :27 doi: / Variableχ2p-value Presence of co-morbid illness Altered consciousness Presence of tachycardia Peripheral edema Hypoalbuminemia Elevated transaminases Acidosis Arterial hypoxemia Hypercapnia Presence of new infiltrates on the chest radiograph Need for invasive ventilation

Table 5 Predictors of death in 116 patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to the intensive care unit: stepwise multivariate logistic regression analysis Mohan et al. BMC Pulmonary Medicine :27 doi: / VariableOdds ratio95% Confidence intervalsp-value Need for invasive ventilation to 3.009p < Presence of co-morbid illness to 0.037p < 0.01 Hypercapnia to 0.010p < 0.05

DISCUSSION Not much info on burden of AE-COPD in ER, its presentation and outcome Significant number of patients (n=53; 45.7%) had co-morbid conditions, and this was a predictor of death Accurate assessment of co-morbid conditions and institution of specific treatments should help to reduce morbidity and mortality Past PTB important cause of COPD and also of AE-COPD (p<0.001) Ramifications in areas where PTB endemic and smoking on the rise High prevalence of respiratory failure in study. Invasive ventilation associated with poor prognosis In conclusion, in addition to host genetic factors, smoking behaviour, accessibility to health care and presence of co-morbid conditions contribute to morbidity and mortality due to AE-COPD