Abbreviations:

APACHE II- Acute Physiology, Age, Chronic Health Evaluation II; APACHE- Acute Physiology, Age, Chronic Health Evaluation; CPIS- Clinical Pulmonary Infection Scoring; VAP- Ventilator Associated Pneumonia; CMV- Continous Mandatory Ventilation; PCV- Pressure Control Ventilation; SIMV- Synchronized Intermittent Mandatory Ventilation;  MHT- Manual Hyperinflation Technique; Na- Sodium; k- Pottasium; Fio2- Fraction Of Inspired Oxygen; Aado2- Alveolar Arterial Oxygen Gradient; PaO2- Partial Pressure of Oxygen; WBC- White Blood Cell; Hct- Hematocrit; LAMA- Leaving Against Medical Advice; mmHg- Millimetre of mercury; mmol/L- Milimoles per litre; mm3- Milimeter per cube; °C- Degree Celsius

1. Introduction

Around the world 19 million cases of sepsis are reported, with 5 million deaths are estimated to be in middle and low income countries due to sepsis [1]. 95% deaths are occurring in low and middle income countries due to maternal sepsis [2]. Sepsis by definition is a ‘life-threatening organ dysfunction caused by a dysregulated host response to infection’ [3]. American college of Chest Physicians and society of critical care medicine established standard principle in classification of sepsis on basis of their symptoms in which Systemic Inflammatory response is define as Core Body temperature > 38°c or < 36 °c, Heart Rate ≥ 90 bpm, Respiratory Rate ≥ 20/min (or PaCO2 <32 mmHg),White blood cells ≥ 12,000/μl or ≤ 4000/μl or >10% immature forms, Sepsis is define on at least 2 or more systemic inflammatory response criteria with underlying infection, Severe sepsis involve sepsis with organ damage, Septic shock involve sepsis with persistent or refractory low blood pressure [4-6]. Proper management of patients diagnosed with sepsis can only be done by knowing rate of mortality [7]. Severity and mortality of Patient admitted in Intensive care unit (Icu) with sepsis can be analyzed by scale i. e. Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) introduced by Knaus et al. in 1985 which was considered as modification of Acute Physiology, Age and Chronic Health Evaluation (APACHE) by removing infrequently used variables like lactate, osmolality [8]. Respiratory Tract Infections frequently leads to sepsis [9]. Other sources of sepsis include urinary tract, abdomen, invasive devices, central nervous system, endocarditis [10].

Ventilator Associated Pneumonia (VAP) is considered as common risk factor frequently associated with intubated sepsis patients [11]. It is common problem in patient intubated for more than 48 hours. Estimated occurrence of ventilator associated pneumonia is around 9-27% of all mechanically ventilated patients [12]. VAP leads to difficulty in weaning off leading to increase financial and medical resources burden. Common risk factors that increase chances of VAP are classified into modifiable factors and non-modifiable factors. Modifiable factors include Prolong Supine Positioning, abdominal distention, colonization in ventilator circuit, low pressure in endotracheal tube cuff circuit while nonmodifiable factors include gender, immunocompromised, history of trauma or disease and old age (over 60 years) [13, 14]. Clinical diagnosis of Ventilator Associated Pneumonia is often difficult due to decreased sensitivity and specificity. Based on 6 parameters, In 1992 Clinical Pulmonary infection score was evolved [14]. As discussed above that any patient intubated for more than 48 hours can develop Ventilator Associated Pneumonia so prevention of ventilator associated pneumonia begins with decreasing time of mechanical ventilation which can only be decreased by using strategies that includes use of Noninvasive positive pressure ventilator [15, 16], avoiding reintubation, early tracheostomy [17] and preventive measures which includes elevation of bed to 45 degree, antimicrobial coated endotracheal tube, endotracheal suctioning [15] . Patients intubated for prolong time are with impaired level of consciousness and absence of cough reflex which shows significant reduction in airway clearance [18]. Passive Chest physiotherapy is commonly used to promote airway clearance, to overcome ventilation perfusion mismatch in mechanically ventilated patient [19, 20]. Passive Chest physiotherapy uses manual techniques that are responsible for sputum clearance and help in preventing lung from atelectasis, air way obstruction, and hyperinflation. Passive Chest Physiotherapy is also responsible for removing infected secretions by decreasing rate of proteolytic tissue damage [21]. Passive chest physiotherapy involves various techniques for external manipulation of thorax. They basically dislodge chest secretions by applying kinetic energy to chest wall [22]. Passive Chest Physiotherapy plays significant role in ICU patients but there was very low data regarding prevention of ventilator associated pneumonia in sepsis patients through passive chest physiotherapy so this study was conducted to assess efficacy of Passive Chest Physiotherapy in Prevention of Ventilator Associated Pneumonia in Sepsis Patients.

2. Methodology

This was a Quasi Experimental study conducted in Liaquat National Hospital from February to October 2019 with convenient based non probability sampling technique. Total 60 patients were included in this study. All those patients intubated for more than 48 hours, diagnosed with sepsis on the basis of American college of chest physicians and society of critical care principle [6] or conditions that leads to sepsis including Urinary Tract Infection, burns,invasive devices, Immunocompromised patients, Acute Kidney Injury, Chronic Kidney disease, End Stage Renal Disease, Diabetic Ketoacidosis, Neurological cases, Poisoning, Post-surgical complications were included in this study while those who suffered from undrained pneumothorax, Pulmonary embolism, pulmonary edema, clotting disorders, osteoporosis of ribs, lung contusion, emphysema, Intra cranial pressure greater than 20 mm hg, hemodynamically unstable patients, myocardial infarction, irregular arrhythmias, hemodialysis, recent open heart surgery, open wounds or skin infections were excluded from this study. Ethical Approval was taken from Institutional Review Board of Liaquat National School Of Physiotherapy before commencement of this study.

Patients included in this study were served with positive pressure ventilator including Continous Mandatory Ventilation (CMV), Pressure Control Ventilation (PCV) and Synchronized Intermittent Mandatory Ventilation (SIMV). Informed consent form was signed by patient’s relative. Informed consent form consisted of purpose of the study as well as description of procedure, All risk and benefits were mentioned in informed consent form . After taking informed consent form from patient’s relative, baseline assessment was done which included Gender, age, diagnosis, comorbid and mode of ventilator used. Acute Physiological Age Chronic Health Evaluation II (APACHE II) And Clinical Pulmonary Infection Scoring (CPIS) scales were used as assessment tools [23]. Acute Physiological Age Chronic Health Evaluation II also known as APACHE II was used for measuring mortality rate of patients [7, 24]. Ayazogu TA in his study showed that sensitivity and specificity of APACHE II for predicting mortality rate was 100% and 86. 6% respectively [25]. APACHE II was based on 12 variables including mean arterial blood pressure, heart rate, temperature, oxygenation, respiratory rate, arterial PH, serum sodium, potassium and creatinine, hematocrit, white blood cell count, and GCS and chronic health, age score. Each variable was ranked from 0-4. APACHE II score ranged from 0-71. Score of 25% represents mortality 50% and score of over 35% represents mortality 80%. APACHE II was calculated during first 24 hours in ICU to predict mortality rate of patients admitted in ICU [26]. APACHE II scoring has been shown in Table 1. Clinical Pulmonary Infection Scoring also known as CPIS scoring was used as diagnostic tool for confirmation of ventilator associated pneumonia with sensitivity of 79% and specificity of 75% as shown in Swoboda SM et al. study [27]. CPIS scoring scale was based on 6 parameters including Temperature, WBC count, tracheal secretions, pulmonary radiography, oxygenation, tracheal culture. Score greater than 6 considered as Likelihood of Ventilator associated pneumonia [14]. CPIS scoring has been shown in Table 2. All 60 patients received same treatment i. e. Passive Chest Physiotherapy. Total days of treatment session were 10 days and twice daily i. e. 11:00 am and 3:30 PM. CPIS scoring was taken in all 10 days to measure difference before initiation of passive chest physiotherapy and at end of passive chest physiotherapy session. Standard care in terms of nursing, drugs, therapies as implemented by doctor was strictly followed throughout the intervention. The treatment of patient was left entirely on decision of senior intensivist or doctor/surgeon. Passive Chest Physiotherapy administered to patients was as follow:

1. Manual Hyperinflation Technique (MHT): It uses technique that delivers deep breaths to patient mechanically ventilated by rebreathing bag [27]. Mapleson Water Circuit of 2L was used. Slow deep inspiration and inspiratory hold at full inspiration was done with both hands to improve collateral ventilation. MHT was carried out twice daily at a rate of 8-13 breaths per minute during 20 minutes session
2. Suctioning: Duration of endotracheal suctioning was limited to 15 seconds [28]. Quickly and gently catheter was passed down tube until obstruction was felt and catheter was withdraw 2cm prior to negative pressure, withdrawing of catheter was done with twisting motion while suctioning intermittently. 1-2 ml of normal saline was used to enhance aspiration of dry secretions. Size of Suction catheter used were 14 and 16. Specimen from Lower respiratory tract was collected in sterile mucous extractor for culture testing. After end of suctioning, bed was elevated to 45 degree to improve ventilation for minimum 30 minutes [29].
3. Percussions: Percussions are defined as rhythmically striking patient’s chest with cupped hand over area of secretion. The patient was position in supine and therapist hands were placed on patient’s chest, Shoulder, elbows and wrist were straight to apply percussion in wavy motion. Percussions duration used was 5 minutes on each lobe twice daily [30].
4. Compressions: Chest compressions are mainly used in mobilization of secretions in central airway from periphery. Patient was positioned supine and therapist placed his fingers over intercostal spaces and shoulder, elbow, wrists were kept straight and compression force was applied at the end of inspiration and start of expiration. Compressions were performed three times on each lobe [30].

Data was analyzed using SPSS 22. 0. Descriptive Statistics was reported. Paired t-test was used to assess the significance. P value of <0. 05 was set as significant level.

Physiologic Variable	Point Score
	+4		+3	+2	+1		0	+1	+2	+3		+4
Temperature	>41	39- 40. 9		-		38. 5- 38. 9	36-38. 4	34-35. 9	32- 33. 9		30- 31. 9	<29. 9
Mean Arterial Pressure (mmHg)	>160	130- 159		110- 129		-	70-109	-	50-60		-	<49
Heart Rate	>180	140- 179		110- 139		-	70-109	-	55-69		40-54	<39
Respiratory Rate	>50	35-49		-		25-34	12-24	10-11	6-9		-	<5
Oxygenation : a)    Fio2 >0. 5 (Use AaDo2) b)    Fio2 <0. 5 (Use PaO2)	>500	350- 499		200- 349		-	<200	-	-		-	-
	-	-		-		-	>70	61-70	-		55-60	<55
Arterial pH	>7. 7	7. 6- 7. 69		-		7. 5- 7. 59	7. 33- 7. 49	-	7. 25- 7. 32		7. 15- 7. 24	<7. 15
Serum Na (mMol/L)	>180	160- 179		155- 159		150- 154	130- 149	-	120- 129		111- 119	<110
Serum K (mMol/L)	>7	6-6. 9		-		5. 5- 5. 9	3. 5-5. 4	3-3. 4	2. 5- 2. 9		-	<2. 5
Serum Creatinine (mg/dl)	>3. 5	2-3. 4		1. 5-1. 9		-	0. 6-1. 4	-	<0. 6		-	-
Hct (%)	>60	-		50-59. 9		46- 49. 9	30-45. 9	-	20- 29. 9		-	<20
WBC (in 1000S)	>40	-		20-39. 9		15- 19. 9	3-14. 9	-	1-2. 9		-	<1
Glasgow Coma Scale (GCS) SCORE= MINUS ACTUAL GCS

Table 1: APACHE II Scoring Scale.

CPIS Points	0	1	2
Tracheal Secretions	Rare	Abundant	Purulent
Leukocyte Count (mm3)	>4,000 and <11000
Temperature °C	>36. 5 or <38. 4	>38. 5 or <38. 9	>39 or <36
Pao2/FIO2 ratio (mmHg)	>240 or ARDS	-	<240 or no ARDS
Chest Radiograph	No Infiltrates	Diffused Infiltrates Infiltrates	Localized
Culture of Tracheal Aspirate	Negative	-	Positive

Table 2: Clinical Pulmonary Infection Scoring.

3. Result

Total 60 patients fulfilled inclusive criteria. Baseline Assessment was measured shown in Table 3. APACHE II was measured during first 24 hours in ICU stay for predicting mortality. Predicted mortality has been Sho-

wn in Table 4. CPIS the main outcome variable was measured before initiation of passive chest physiotherapy and after 10^th day of passive chest physiotherapy which showed that chances of ventilator associated pneumonia was 32 (53. 3%) before initiation of passive chest physiotherapy while on 10th day chances of ventilator associated pneumonia decreased to 2 (3. 3%). Passive Chest Physiotherapy was statistically significant in decreasing chances of ventilator associated pneumonia, shown in table 5. On 10^th day

 after passive chest physiotherapy out of 60 patients 37 (61. 7%) were extubated, died patients were 3 (5%), Leaving against Medical authority (lama) were 3 (5%) and 17 (28. 3%) were on ventilator at 10 day shown in Graph 1. Mortality rate was found to be decreased on 10th day after passive chest physiotherapy (0. 05 ± 0. 22). Mortality rate has been shown in table 6 and graph 2.

Variables		Mean ± S. D / n (%)
Age (years)		41. 58 ± 12. 93
Gender	Male	38 (63. 3%)
	Female	22 (36. 7%)
Comorbid	Hypertension (HTN)	11 (18. 3%)
	Diabetes	8 (13. 3%)
	No Known Comorbid	19 (31. 7%)
	More than 1Comorbid	22 (36. 7%)
Type Of ICU Stay	Medical Icu	18 (31%)
	Surgical Icu	10 (17. 2%)
	Nephrology Icu	11 (19. 2%)
	Chest Icu	11 (19. 2%)
	Neurology Icu	4 (6. 9%)
	Cardiac Icu	4 (6. 9%)
Mode Of Ventilator	CMV	34 (58. 6%)
	SIMV	17 (29. 3%)
	PCV	7 (12. 1%)
APACHE II		1. 38 ±0. 49

{Data are presented as mean?±?SD or number (%)}

Table 3: Characteristics Of Baseline Assessment.

Variable	n%
0% mortality	37 (61. 7%)
80% mortality	23(38. 3%)

{Data are presented as number (%)}

Table 4: Frequency of Mortality Rate using APACHE II.

Variable	CPIS Score Mean ± S. D		P-Value
Passive Chest Physiotherapy	Before passive chest physiotherapy	1. 53 ± 0. 50	0. 03
	10 Days after Passive Chest Physiotherapy	1. 28 ± 0. 78

{Data are presented as mean±SD}

Table 5: Descriptive statistics for Clinical Pulmonary Infection Scoring.

on ventilator

LAMA

died

extubated

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

Variable	Mean +- S. D	p-value
APACHE II during first 24 hours	1. 38 ± 0. 49	0. 00
Mortality Rate On 10th day after Passive Chest Physiotherapy	0. 05 ± 0. 22

{Data are presented as mean?±SD}

Table 6: Descriptive Statistics Of Mortality Rate.

5. Discussion

This was a quasi-experimental study designed to assess the impact of passive chest physiotherapy in prevention of ventilator associated pneumonia in sepsis. We included patients diagnosed with sepsis or condition that could lead to sepsis, with intubation more than 48 hours Patients included in this study were all treated with passive chest physiotherapy twice daily in total 10 days. This study revealed that mortality rate was significantly decreased at 10th day after passive chest physiotherapy i. e. 3 (5%). Nakagawa NK et al. in their study revealed that immobility in intensive care leads to impaired mucocilliary clearance [31]. Castro et al. [32] in their study showed that Passive Chest physiotherapy included body positioning, percussions and suctioning was significantly effective in decreasing duration of mechanically ventilated patients and decreasing chances of respiratory infections. In our study chances of ventilator associated pneumonia was significantly decreased to 2% (0. 03). Wang TH et al. [33] in their study showed that intensive chest physiotherapy was effective in preventing reintubation (0. 01) and was effective in decreasing rapid shallow breathing index while in our study we found that 31 (61. 7%) were extubated after 10 days passive chest physiotherapy. Grap M et al. [34] in their study revealed that 30 to 45 degree of bed elevation was effective in early preventive measure of ventilator associated pneumonia. Yang M et al. [22] in their study showed that APACHE was useful in predicting mortality of patients diagnosed with ventilator associated pneumonia (0. 00) and CPIS was also found to be useful in diagnosing ventilator associated pneumonia (0. 02). We observed that passive chest physiotherapy was effective in decreasing mortality rate of patients diagnosed with sepsis (0. 00). dos Santos RS et al. [35] in their study showed that  passive chest physiotherapy was effective in decreasing lactate (0. 00) and increasing PaO2 (0. 03) after 15 minutes in Septic Shock Patients. Pattanshetty RB et al. [36]. in their study showed that multimodality passive chest physiotherapy twice daily including Manual Hyper Inflation and suctioning was effective in prevention of ventilator associated pneumonia (0. 00) and weaning was successful in 62% patients in the control group receiving Manual Hyperinflation and suctioning. Limitations of this current study were quite few which were that we used convenience based sampling from only 1 hospital, which may not be representative of the entire population . No blinding was held during the entire course of the study.

5. Conclusion

Results of this study showed that passive chest physiotherapy was effective in preventing Ventilator Associated Pneumonia in Sepsis Patient; there was significant decrease in mortality rate after passive chest physiotherapy when compared with before initiation of passive chest Physiotherapy. Further Studies in term of Large Sample size are required to confirm the effectiveness of passive chest physiotherapy in prevention of VAP in Sepsis Patients. Furthermore, this study can be helpful for Physiotherapists to carry out their responsibilities in the ICU in a more professional manner in future. Several patients in the Intensive Care Unit (ICU) suffer from sepsis, which leads to ventilator associated pneumonia among them.  By  using Passive Chest Physiotherapy we can reduce patients' dependency on ventilators and help in their early discharge from hospitals, help reduce patients' dependency on medicines to a great extent, and bring down the rate of mortality in sepsis, which is quite high in the country.

Conflict of Interest

Author had no conflict of interest

Funding

No funding Received.

Acknowledgment

We are grateful to Dr Zunaira Rais , Dr SM Nadeem Khursheed and Ms Farah deeba who provided their expertise that were very helpful for data collection in this research. We would like to show our gratitude to Mr Sohail Muneer, Mr Farhat Fawad, Mr Amjad Hussain and Ms Sana Noman for sharing their pearls of wisdom with us during critical review of this research.

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