Tarun Kumar Dutta

Ventilator-associated pneumonia: A review

Ventilator-associated pneumonia (VAP) is the most frequent intensive-care-unit (ICU)-acquired infection, with an incidence ranging from 6 to 52% [1,2,3,4]. Several studies have shown that critically ill patients are at high risk for getting such nosocomial infections [3,4]. VAP continues to be a major cause of morbidity, mortality and increased financial burden in ICUs [5,6,7,8]. Over the years there has been a significant advance in our understanding of ventilator associated pneumonia. This article reviews the various aspects of VAP such as definition, risk factors, etiological agents, diagnosis, treatment and prevention with emphasis on the recent advances.

Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population.

Though the incidence of hypertension has increased considerably in recent years, the pathophysiologic mechanism that causes progression from stage of prehypertension to hypertension has not been fully elucidated. Therefore, the present study was conducted to assess the sympathovagal imbalance in prehypertensives and hypertensives by spectral analysis of heart rate variability (HRV) to understand the nature of change in autonomic balance in this common dysfunction of mankind. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), and spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), the number of interval differences of successive NN intervals greater than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives (n = 32), prehypertensives (n = 28), and hypertensives (n = 31). Sympathovagal balance was analyzed and correlated with BMI, BHR, and BP in all the groups. It was observed that autonomic imbalance in prehypertensives was due to proportionate increased sympathetic activity and vagal inhibition, whereas in hypertensives, vagal withdrawal was more prominent than sympathetic overactivity. The LF-HF ratio, the sensitive indicator of sympathovagal balance, was significantly correlated with BMI, BHR, and BP. It was concluded that vagal inhibition plays an important role in the critical alteration of sympathovagal balance in the development of clinical hypertension in prehypertensive subjects.

Ventilator-associated pneumonia: role of colonizers and value of routine endotracheal aspirate cultures

OBJECTIVES To determine the role of colonizers in the causation of ventilator-associated pneumonia (VAP) and the value of routine pre-VAP endotracheal aspirate (EA) cultures in appropriately treating VAP. METHODS A prospective observational cohort study was conducted over a period of 15 months. Two hundred patients on mechanical ventilation for>48h were studied. RESULTS Acinetobacter spp (33.7%) and Pseudomonas spp (29.8%) were the most common colonizers. Of the 200 patients, 36 developed VAP. In 20 VAP patients, the pre-VAP EA culture-based strategy was not useful. However, in the remaining 16 VAP patients, a pre-VAP EA culture-based strategy would have appropriately treated 13 (81%; 95% confidence interval (CI) 62-100%), in comparison to only nine (56%; 95% CI 32-80%) by the American Thoracic Society (ATS) strategy. The seven patients in whom the ATS guidelines were inappropriate had Acinetobacter spp and Pseudomonas spp resistant to the higher antibiotics recommended by the ATS for multidrug-resistant pathogens. The positive predictive values of Pseudomonas aeruginosa, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) isolated from pre-VAP EA cultures were 88%, 83%, and 100%, respectively. CONCLUSION VAP patients should be treated based on ATS guidelines, but whenever P. aeruginosa, A. baumannii, and MRSA are isolated from pre-VAP EA cultures, the initial antibiotic therapy should be extended to treat these.

Gender specific association of endothelial nitric oxide synthase gene (Glu298Asp) polymorphism with essential hypertension in a south Indian population

BACKGROUND Endothelial derived nitric oxide (NO) plays a major role in blood pressure regulation. The role of missense variant eNOS-Glu298Asp has been demonstrated by many studies with conflicting results. Our objective was to investigate the association of eNOS gene polymorphism with essential hypertension in a south Indian population. METHODS We carried out a case control study in 438 hypertensive patients and 444 healthy control subjects in a homogenous population. Genotyping was done by PCR-RFLP method. Multiple logistic regression analysis was used to detect the association between genotype and hypertension. RESULTS The homozygous variant genotype Asp298Asp was significantly associated with hypertension (odds ratio 2.4; 95% CI, 1.23-5.0, p<0.01). Gender specific analysis showed both the heterozygous (odds ratio, 2.0; 95% CI, 1.3-2.9, p<0.01) and homozygous variants (odds ratio, 7.9; 95% CI, 2.0-4.1, p<0.001) were positively associated with hypertension in females. The variant allele Asp was higher in female hypertensives when compared to male hypertensive cases (22% vs. 16%). CONCLUSION The eNOS gene polymorphism is a candidate gene for hypertension and the association to be gender specific with respect to females in a south Indian Tamilian population.

Sympathovagal imbalance contributes to prehypertension status and cardiovascular risks attributed by insulin resistance, inflammation, dyslipidemia and oxidative stress in first degree relatives of type 2 diabetics.

Background Though cardiovascular (CV) risks are reported in first-degree relatives (FDR) of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI) with CV risks in these subjects. Subjects and Methods Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104). Results BMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI) were significantly increased (p<0.0001) in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001) and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128–5.326, p = 0.002) of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group. Conclusion SVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics.

Body mass index contributes to sympathovagal imbalance in prehypertensives.

BackgroundThe present study was conducted to assess the nature of sympathovagal imbalance (SVI) in prehypertensives by short-term analysis of heart rate variability (HRV) to understand the alteration in autonomic modulation and the contribution of BMI to SVI in the genesis of prehypertension.MethodsBody mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP) and HRV indices such as total power (TP), low-frequency power (LF), normalized LF (LFnu), high-frequency power (HF), normalized HF (HFnu), LF-HF ratio, mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), standard deviation of normal to normal RR interval (SDNN), the number of interval differences of successive NN intervals greater than 50 ms (NN50) and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives having normal BMI (Group 1), prehypertensives having normal BMI (Group 2) and prehypertensives having higher BMI (Group 3). SVI was assessed from LF-HF ratio and correlated with BMI, BHR, BP and RPP in all the groups by Pearson correlation. The contribution of BMI to SVI was assessed by multiple regression analysis.ResultsLF and LFnu were significantly increased and HF and HFnu were significantly decreased in prehypertensive subjects in comparison to normotensive subjects and the magnitude of these changes was more prominent in subjects with higher BMI compared to that of normal BMI. LF-HF ratio, the sensitive indicator of sympathovagal balance had significant correlation with BMI (P = 0.000) and diastolic blood pressure (DBP) (P = 0.002) in prehypertensives. BMI was found to be an independent contributing factor to SVI (P = 0.001) in prehypertensives.ConclusionsIt was concluded that autonomic imbalance in prehypertensives manifested in the form of increased sympathetic activity and vagal inhibition. In prehypertensives with higher BMI, vagal withdrawal was predominant than sympathetic overactivity. Magnitude of SVI (alteration in LF-HF ratio) was linked to changes in BMI and DBP. BMI had an independent influence on LF-HF ratio. It was advised that life-style modifications such as yoga and exercise would enable achieve the sympathovagal balance and blood pressure homeostasis in prehypertensives.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short‐term (5 min) heart rate variability (HRV) provides a non‐invasive probe of autonomic regulation of sino‐atrial (SA) node automaticity.

IS ADULT DEFINITION OF ANEMIA APPLICABLE TO A GERIATRIC POPULATION? STUDY OF ERYTHROCYTE PARAMETERS IN INDIAN GERIATRIC INPATIENTS

To the Editor: Although Kamal-Bahl et al. demonstrated that elderly patients commonly use propoxyphene, the authors stated that the use of propoxyphene is inappropriate for this population. Unfortunately, such statements are typical of long-standing misconceptions about propoxyphene. First, although the authors effectively employ 1998 Medicare Current Beneficiary Survey data, they neither provide epidemiological evidence of widespread detrimental effects associated with the proper use of propoxyphene nor cite references solidly demonstrating such purported effects. Second, the authors base their assumption on the works of Beers et al., consensus publications that have significant methodological flaws, designed to fault only propoxyphene for adverse effects attributable to the entire class of opioids. The Kamal-Bahl et al. study is but the most recent study among many that systematically exhibits these flaws. A likely reason that some practitioners have considered propoxyphene inappropriate for elderly patients may be because it is believed to increase the probability of falls. Yet, in a recent survey of more than 8,000 community-dwelling women aged 65 and older, multivariate analyses show that opioids are not associated with an increased likelihood of falls. As a rheumatologist with 25 years of clinical experience, I have treated many thousands of patients, approximately 60% of whom are aged 65 and older. I have used propoxyphene in many of these patients, achieving acceptable analgesic efficacy with only rare adverse experiences. By and large, except for occasional dose modifications for the extremely elderly, frail, or chronically ill, my patients tolerate full therapeutic doses. Propoxyphene, especially in combination with acetaminophen, is a safe, effective analgesicFa proven, established agent in the physician’s armamentarium against pain. Few analgesics have demonstrated 40-plus-year histories of safety and efficacy in elderly patients. Terms such as ‘‘inappropriate prescribing’’ need to be based on results of controlled clinical studies or outcomes research in which risks outweigh benefits. Dr. Morton serves on the advisory board of aaiPharma, Inc. (Wilmington, NC), which markets propoxyphene.

Sympathovagal imbalance in young prehypertensives: importance of male-female difference.

Introduction:Although the prevalence of prehypertension is high, the pathophysiological mechanisms and the effects of gender in its causation have not yet been fully understood. Methods:Body mass index, waist-to-hip ratio, basal heart rate, blood pressure, rate pressure product and spectral indices of heart rate variability were reordered and analyzed in young normotensive (n = 344) and prehypertensive (n = 69) subjects. Each group was categorized into male and female subgroups. Results:Ratio of low-frequency to high-frequency powers (LF-HF ratio) of heart rate variability spectrum, the sensitive marker of sympathovagal imbalance (SVI), was significantly more increased (P < 0.001) in male prehypertensives compared with female prehypertensives. Although SVI in prehypertensives was found to be due to both sympathetic activation in the form of increased low-frequency power normalized (increased LFnu) and vagal inhibition in the form of decreased high-frequency power normalized (decreased HFnu), contribution of vagal withdrawal was more in males. LF-HF ratio was significantly correlated with body mass index, waist-to-hip ratio, basal heart rate, blood pressure and rate pressure product by Pearson correlation analysis. Furthermore, multiple regression analysis demonstrated an independent relationship between LF-HF ratio and gender (P = 0.000) and prehypertension status (P = 0.000) in both normotensives and prehypertensives. Conclusions:Vagal inhibition plays an important role in addition to sympathetic activation in alteration of SVI in the genesis of prehypertension, especially in males. Gender and prehypertension status play important role in the causation of SVI. It was suggested that vagal tone of prehypertensives should be maintained at a higher level to prevent their further rise in blood pressure.

Candidate Gene Polymorphisms of Renin Angiotensin System and Essential Hypertension in a South Indian Tamilian Population

Abstract Genetic variants of renin angiotensin system (RAS) gene play a significant role in the pathogenesis of essential hypertension and cardiovascular diseases. In the present study, we investigated the association of RAS gene polymorphisms with hypertension by analyzing the polymorphisms ACE ID, AGT T207M, M268T and AGT1R A1166C in 462 hypertensive patients and 444 healthy subjects. Genotyping was determined by allele specific PCR, PCR-RFLP and RT-PCR Taqman assay. The ACE ID heterozygous (OR=1.5: 95% CI: 1.0-2.3, p < 0.05) and ACE DD homozygous genotype (OR=1.7: 95% CI: 1.2-2.8, p<0.01) was found to be significantly associated with hypertension. There was no significant association between AGT T207M, M268T and AGT1R A1166C gene polymorphisms and hypertension. Gender-specific analysis showed ACE ID heterozygous genotypes were positively associated with hypertension among male hypertensives (OR=1.9: 95% CI: 1.1-2.6, p<0.01). Significant gene-gene interaction was observed between ACE ID and AGT M268T polymorphisms (OR=2.0; 95% CI: 1.2-3.5, p<0.01). Our results suggest that ACE ID polymorphism is associated with hypertension. Further, gene-gene interaction between ACE ID and AGT M268T gene polymorphisms further modified the risk of essential hypertension.