Correlation of Arterial blood gas value in outcome of patient admitted with acute exacerbation of Chronic Obstructive Pulmonary Disease

Introduction: The outcome of Chronic Obstructive Pulmonary Disease depends upon the partial pressure of oxygen and carbon dioxide This study was aimed to �nd the role of arterial blood gas parameters during the length of hospital stay among patients admitted for COPD with acute exacerbation. Materials and Methods: This was an observational study conducted in KIST Medical College Teaching Hospital from February 2017 to August 2019. Patients admitted with chronic obstructive pulmonary disease were evaluated. Demographic data as well as SPO 2 , pulmonary function test, and arterial blood gas analysis were recorded and analyzed. Results: Among 112 patients, the female to male ratio was 1.38: 1 with 84.8% over 60 years of age. One-third of patients (n = 38) had exposure to both tobacco smoking and biomass and of them, 86.8% were females. Mean SpO 2 was 75.9% and mean FEV1 was 0.92 L (SD = 0.295) and signi�cant association was found (p < 0.001) between them. Furthermore, 70 (62.5%) patients had type I respiratory failure and 42 patients (37.5%) had type II respiratory failure. Patients with type II respiratory failure and hypercapnic patients had prolonged hospital stay with signi�cant p-value (p < 0.001). Similarly, signi�cance was observed in the p-value for blood pH, which was < 0.05. Conclusions: Increased length of hospital stay is seen in patients with AECOPD with type II respiratory failure. Hence, aggressive early management to correct hypercapnia may lead to decreased hospital stay along with a better outcome. Thus hypercapnia should be considered as one of the important criteria to �ag the patient and manage accordingly.


Introduction
Chronic obstructive pulmonary disease (COPD) is a common noncommunicable disease, with a strong association with cigarette smoking and exposure to household smoking.The national data of 2017 showed that, among noncommunicable diseases, COPD was the 2nd most common cause of death (9.8% of total deaths) only preceded by Ischemic heart disease.[5] Due to its chronicity, physical disability, and disease-associated mortality, its impact on the health economy is considerable.
In 2016, 251 million cases of COPD have been reported globally by the Global Burden of Disease Study reports.[1] The mortality rate due to COPD, in 2015, is estimated to be 3.17 million world-wide comprising approximately 5% of all deaths.[1]The highest prevalence rate was estimated in the American continent (15.2% in 2010).In East Asia, the estimated prevalence of COPD is as compared to South Asia, which is 9.7% in 2010.This gure is the lowest across the globe.[2] More than 90% of COPD deaths occur in low and middle-income countries.[1] World Health Organization (WHO) report on the global tobacco epidemic projected a 160% increment in COPD-associated mortality in the Southeast Asian region.[3] The prevalence of COPD is in a decreasing trend but remains very high.[4] Several risk factors attributing to the poor outcome on a stable COPD patient have been identi ed.Among them, forced expiratory volume in 1 second (FEV 1 ) [6], body mass index, and exercise tolerance are established.[7] Besides these factors, infections also play a pivotal role.The BODE Index was designed to assess COPD prognosis [8]which included BMI, FEV 1 , a modi ed Medical Research Council dyspnoea score, and the 6-min walk distance.Overall, the BODE Index was more effective than FEV 1 alone at predicting the risk of all-cause or respiratory mortality [9] Amongst chronic obstructive respiratory complications, respiratory failure is a frequent occurrence.The presence or absence of hypoxemia/hypercapnia dictates the good or worse outcome of the disease process.[10] Hence, identi cation of the various factors and their association may enable clinicians to assess the life expectancy of the patient much better.This is extremely important, to implement more individualised and effective treatment strategies.
The current study aimed to investigate the arterial blood gas parameters as a factor associated with the length of hospital stay of patients admitted for COPD with acute exacerbation.

Materials And Methods
This was a prospective, observational study conducted in the Department of Internal Medicine and Pathology, KIST Medical College Teaching Hospital.After approval from the Institutional Review Board-KIST Medical College, data were collected from the patients admitted with the diagnosis of acute exacerbation of COPD (AECOPD) from February 2017 to August 2019.Any known patient with COPD presenting with a sustained increase in cough, sputum production, and/or dyspnea was considered as AECOPD.The patients were explained regarding the research and written consent was obtained.Patients not requiring all the necessary investigations or not willing to participate were excluded from the study.
A proforma including social demographics, history of associated diseases, smoking history, house-hold smoke exposure, and clinical ndings of crepitation, wheeze, SPO 2 , blood pressure was developed.Investigations done were total leukocyte count with differential count, pulmonary function test, and arterial blood gas analysis, sputum/blood/urine culture Also included in proforma were the use of steroids and the total day of hospital stay.These ndings were collected, entered, and analyzed in a proforma, Microsoft Excel, and SPSS v. 23 respectively.
Percentage, mean, correlation, and Logistic Regression were analyzed.P-value was calculated with the Chi-square test and p-value < 0.05 were considered signi cant.

Results
During the study period, a total of 203 patients of COPD were admitted to the medical department of KIST Medical College Teaching Hospital.Among these patients, 112 patients either consented for involvement in the study or met the inclusion criteria.Of these 112 study population, 47 were male and 65 female, with female to male ratio of 1.38: 1.
Most of the patients were older than 60 years (n = 95; 84.8%) and besides, 25 patients (22.3%) were older than 79 years.Age ranged from 43 years to 93 years with a mean age of 69.65 years.(Table 1) Among the male, 30 out of 47 (63.8%) were between 60 and 79 years.Likewise, in the female group, 40 out of 65 (61.5%) were between 60 and 79 years.The majority of the patients were smokers, with only 6 (5.4%) non-smoker.Our, 38 patients (33.9%) had exposure to both tobacco smoking and biomass while cooking and heating, of which 33 (86.8%) were female and only 5 (13.2%) were male.44 patients (39.3%) were still using biomass for cooking and heating purpose.Regarding smoking, most of the patients smoked 10 to 14 sticks per day (n = 48, 42.8%), whereas those smoking > 14/day were only 25% (n = 28).
All the males and the majority of females in the study population were tobacco smokers.Only 6 out of 65 (9.2%) females were non-smokers.( Logistic regression was performed to see the effect of ABG in the duration of hospital stay for which 5 days cut off value was considered.The type of respiratory failure and pH of blood showed signi cant ndings.The patients without respiratory failure were discharged earlier (5.09days) than type I respiratory failure and type II respiratory failure (Table 4) with signi cant p-value (p < 0.001).Similarly, the p-value for blood pH was < 0.05.

Discussion
COPD is one of the major public health problems around the world and acute exacerbation of COPD is the major cause of signi cant morbidity and mortality worldwide.Though the prevalence varies in different countries along with the age and sex of an individual, COPD is going to be the fth leading cause of disability and the third leading cause of death worldwide by 2020.[11] According to the study conducted by Dhimal et al in a different part of Nepal, the Prevalence of COPD was 11.7%.[12] Respiratory failure is a common and important event, which is frequently associated with severe exacerbations of COPD.[13] The higher mortality rate is associated with the presence of hypercapnia in respiratory failure.[14] Changes in lung mechanics are believed to be the signi cant determinants of the physiological variations from the norm that describe hypercapnic respiratory failure.A subject would need to expand their ventilation to overcome the wasted ventilation in high ventilation/perfusion ratio units, however, their failure to do so regardless of the respiratory boost that a rising CO 2 strain gives has been the subject of a lot of discussions.[15] In this study, among 112 patients, 47 (41.96%) were male and 65 (58.04%)female.Similar ndings were observed in a study done by Ghosh V et al. which had 59.6% female patients in comparison to 40.4% male patients.[16]One reason could be increased exposure to biomass among females, due to involvement in household cooking.In contrast, Dhimal et al, in their study, concluded male predominance among patients with COPD.[12] The plausible hypothesis regarding increased incidence among females might be a genetic predisposition for smoking-related lung changes in certain families.Silverman et al, in his study of 84 probands, not only observed high prevalence among females (71.4%) but also had an almost double risk of having obstructive lung disease.[17] Studies with an animal had shown the role of Estrogen in the metabolism of tobacco-smoke.In the animal model; estrogen upregulated the cytochrome p-450 enzymes; which plays a role in increasing susceptibility to cigarette smoke-related oxidant injury in the lung parenchyma.[17] Anatomically, Females have smaller lung and airways compared to males, hence, with the same amount of exposure to smoking they are more prone to develop the disease.
Cigarette smoking is a well-established cause for COPD followed by biomass exposure in a country like Nepal and India.[4,18] Among the study population, 94.6% were smoker whereas the rest were non-smokers.33.9% (n = 38) patients had a history of both tobacco smoking and biomass exposure of which 33 (86.8%) were female whereas only 5(13.2%) were male.Among 112 patients, 39.3% of patients still had a history of biomass exposure.Among total study patients, all male patients were tobacco smokers whereas only 9.23% of females were non-smokers.
A signi cant association between SpO 2 and FEV 1 was found (p < 0.001), unlike other studies where there was no signi cant correlation between FEV 1 % predicted and SpO 2 values.[19,20] FEV 1 value was compared with the hospital stay which showed a consistent and important association of decreasing FEV 1 (increasing severity of COPD stage) with the prolonged hospital (p-value − 0.004).A similar nding was found in the study done by Sijapati et al. [21] In this study, as compared to Type 1 respiratory failure, the patients with type 2 respiratory failure had prolonged hospital stay (p < 0.001) (Table 4).This may be because of the intervention needed to washout the CO 2 utilizing either Invasive or non-invasive ventilator supports.Other studies also have ndings similar to ours.[14,21,22] A study done by Nousheen et al observed that hypercapnic patients had a longer hospital stay (mean 9.27 ± 7.57 days), increased requirement for non-invasive mechanical ventilation on admission (n = 45 (78.94%)) and longer mean time to clinical stability (4.39 ± 2.0 days) compared with the other groups.[23] Hypercapnic patients had a longer duration of hospital stay in comparison to normocapnic patients (Table 3 ).
Among 61.6% of our patients receiving steroids, no signi cant change in the duration of hospital stay was observed (p > 0.05).Scholl et al, in his study done at Colorado Hospital between July 1, 2012, and May 20, 2016, included AECOPD patients (89 in the steroid group and 49 in the non-steroid group).No signi cant difference was seen in the mean duration of hospital stay (4.7 ± 3.2 versus 4.2 ± 2.1 days, p = 0.27).[24] In contrary to this and our study, Woods et al experienced a signi cantly shorter length of hospital stay in comparison to placebo (8.5 versus 9.7 days, P = 0.03).(25) The role of steroids in the length of hospital stay has to be studied further.

Conclusions
COPD is a complex and progressive lung disease associated with signi cant morbidity and mortality.Increased length of hospital stay is seen in hypercapnic patients suffering from AECOPD with type II respiratory failure.Hence, aggressive early management to correct hypercapnia may lead to a shortened hospital stay and thus, better outcome.For that, type II respiratory failure should be considered as one of the important criteria to ag the patient and manage accordingly.However, further large scale studies are required to con rm the observed ndings of this study.

Declarations
Ethics approval and consent to participate:

Table 1
Demographic and other relevant ndings among the study population (n = 112)

Table 1 )
SpO 2was evaluated in all the patients in the study with a mean SpO 2 of 75.9% (SD ± 12.01).In pulmonary function tests, mean FEV 1 was 0.92 L (SD = 0.295) with a minimum of 0.20 L and maximum 1.61 L. (Table1) Similarly, mean FVC was 1.44 L (SD ± 0.485) with a minimum of 0.29 L and maximum 2.90 L and mean FEV 1 /FVC ratio was 0.64 (SD ± 0.058) with a minimum of 0.45 and maximum 0.73.Decreased SpO 2 was observed in patients with low FEV 1 (p < 0.001).Among the study population 30 patients (26.8%) had leucocytosis and 3 patients (2.7%) had Leukopenia.

Table 2
Age and gender-wise ndings of arterial blood gas tests among the study population (n = 112) effusion.13(11.6%)patientswere microbial culture-proven, infective cases, whereas 99 (88.4%) had a negative microbial culture.Various variables were correlated with the number of hospital stays.Mean hospital stay was 7.48 days (SD ± 2.73) with a minimum of 4 days and a maximum of 13 days.There was no signi cant difference in the duration of hospital stay in both males and females (M = 7.06 days vs. F = 7.78 days).A signi cant correlation was observed with the pCO 2 level and length of hospital stay with a p-value < 0.001.(Table3)Similarly, a signi cant correlation was observed between PO 2 and hospital stay (p < 0.05).

Table 4
Mean hospital stay among various arterial blood gas ndings