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1.  Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
The objective of this evidence-based analysis was to examine the effectiveness, safety, and cost-effectiveness of noninvasive positive pressure ventilation (NPPV) in the following patient populations: patients with acute respiratory failure (ARF) due to acute exacerbations of chronic obstructive pulmonary disease (COPD); weaning of COPD patients from invasive mechanical ventilation (IMV); and prevention of or treatment of recurrent respiratory failure in COPD patients after extubation from IMV.
Clinical Need and Target Population
Acute Hypercapnic Respiratory Failure
Respiratory failure occurs when the respiratory system cannot oxygenate the blood and/or remove carbon dioxide from the blood. It can be either acute or chronic and is classified as either hypoxemic (type I) or hypercapnic (type II) respiratory failure. Acute hypercapnic respiratory failure frequently occurs in COPD patients experiencing acute exacerbations of COPD, so this is the focus of this evidence-based analysis. Hypercapnic respiratory failure occurs due to a decrease in the drive to breathe, typically due to increased work to breathe in COPD patients.
There are several treatment options for ARF. Usual medical care (UMC) attempts to facilitate adequate oxygenation and treat the cause of the exacerbation, and typically consists of supplemental oxygen, and a variety of medications such as bronchodilators, corticosteroids, and antibiotics. The failure rate of UMC is high and has been estimated to occur in 10% to 50% of cases.
The alternative is mechanical ventilation, either invasive or noninvasive. Invasive mechanical ventilation involves sedating the patient, creating an artificial airway through endotracheal intubation, and attaching the patient to a ventilator. While this provides airway protection and direct access to drain sputum, it can lead to substantial morbidity, including tracheal injuries and ventilator-associated pneumonia (VAP).
While both positive and negative pressure noninvasive ventilation exists, noninvasive negative pressure ventilation such as the iron lung is no longer in use in Ontario. Noninvasive positive pressure ventilation provides ventilatory support through a facial or nasal mask and reduces inspiratory work. Noninvasive positive pressure ventilation can often be used intermittently for short periods of time to treat respiratory failure, which allows patients to continue to eat, drink, talk, and participate in their own treatment decisions. In addition, patients do not require sedation, airway defence mechanisms and swallowing functions are maintained, trauma to the trachea and larynx are avoided, and the risk for VAP is reduced. Common complications are damage to facial and nasal skin, higher incidence of gastric distension with aspiration risk, sleeping disorders, and conjunctivitis. In addition, NPPV does not allow direct access to the airway to drain secretions and requires patients to cooperate, and due to potential discomfort, compliance and tolerance may be low.
In addition to treating ARF, NPPV can be used to wean patients from IMV through the gradual removal of ventilation support until the patient can breathe spontaneously. Five to 30% of patients have difficultly weaning. Tapering levels of ventilatory support to wean patients from IMV can be achieved using IMV or NPPV. The use of NPPV helps to reduce the risk of VAP by shortening the time the patient is intubated.
Following extubation from IMV, ARF may recur, leading to extubation failure and the need for reintubation, which has been associated with increased risk of nosocomial pneumonia and mortality. To avoid these complications, NPPV has been proposed to help prevent ARF recurrence and/or to treat respiratory failure when it recurs, thereby preventing the need for reintubation.
Research Questions
What is the effectiveness, cost-effectiveness, and safety of NPPV for the treatment of acute hypercapnic respiratory failure due to acute exacerbations of COPD compared with
usual medical care, and
invasive mechanical ventilation?
What is the effectiveness, cost-effectiveness, and safety of NPPV compared with IMV in COPD patients after IMV for the following purposes:
weaning COPD patients from IMV,
preventing ARF in COPD patients after extubation from IMV, and
treating ARF in COPD patients after extubation from IMV?
Research Methods
Literature Search
A literature search was performed on December 3, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), Wiley Cochrane, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until December 3, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.
Since there were numerous studies that examined the effectiveness of NPPV for the treatment of ARF due to exacerbations of COPD published before 2004, pre-2004 trials which met the inclusion/exclusion criteria for this evidence-based review were identified by hand-searching reference lists of included studies and systematic reviews.
Inclusion Criteria
English language full-reports;
health technology assessments, systematic reviews, meta-analyses, and randomized controlled trials (RCTs);
studies performed exclusively in patients with a diagnosis of COPD or studies performed with patients with a mix of conditions if results are reported for COPD patients separately;
patient population: (Question 1) patients with acute hypercapnic respiratory failure due to an exacerbation of COPD; (Question 2a) COPD patients being weaned from IMV; (Questions 2b and 2c) COPD patients who have been extubated from IMV.
Exclusion Criteria
< 18 years of age
animal studies
duplicate publications
grey literature
studies examining noninvasive negative pressure ventilation
studies comparing modes of ventilation
studies comparing patient-ventilation interfaces
studies examining outcomes not listed below, such as physiologic effects including heart rate, arterial blood gases, and blood pressure
Outcomes of Interest
intubation rates
length of stay (intensive care unit [ICU] and hospital)
health-related quality of life
duration of mechanical ventilation
weaning failure
NPPV tolerance and compliance
Statistical Methods
When possible, results were pooled using Review Manager 5 Version 5.1, otherwise, the results were summarized descriptively. Dichotomous data were pooled into relative risks using random effects models and continuous data were pooled using weighted mean differences with a random effects model. Analyses using data from RCTs were done using intention-to-treat protocols; P values < 0.05 were considered significant. A priori subgroup analyses were planned for severity of respiratory failure, location of treatment (ICU or hospital ward), and mode of ventilation with additional subgroups as needed based on the literature. Post hoc sample size calculations were performed using STATA 10.1.
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
NPPV for the Treatment of ARF due to Acute Exacerbations of COPD
NPPV Plus Usual Medical Care Versus Usual Medical Care Alone for First Line Treatment
A total of 1,000 participants were included in 11 RCTs1; the sample size ranged from 23 to 342. The mean age of the participants ranged from approximately 60 to 72 years of age. Based on either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria or the mean percent predicted forced expiratory volume in 1 second (FEV1), 4 of the studies included people with severe COPD, and there was inadequate information to classify the remaining 7 studies by COPD severity. The severity of the respiratory failure was classified into 4 categories using the study population mean pH level as follows: mild (pH ≥ 7.35), moderate (7.30 ≤ pH < 7.35), severe (7.25 ≤ pH < 7.30), and very severe (pH < 7.25). Based on these categories, 3 studies included patients with a mild respiratory failure, 3 with moderate respiratory failure, 4 with severe respiratory failure, and 1 with very severe respiratory failure.
The studies were conducted either in the ICU (3 of 11 studies) or general or respiratory wards (8 of 11 studies) in hospitals, with patients in the NPPV group receiving bilevel positive airway pressure (BiPAP) ventilatory support, except in 2 studies, which used pressure support ventilation and volume cycled ventilation, respectively. Patients received ventilation through nasal, facial, or oronasal masks. All studies specified a protocol or schedule for NPPV delivery, but this varied substantially across the studies. For example, some studies restricted the amount of ventilation per day (e.g., 6 hours per day) and the number of days it was offered (e.g., maximum of 3 days); whereas, other studies provided patients with ventilation for as long as they could tolerate it and recommended it for much longer periods of time (e.g., 7 to 10 days). These differences are an important source of clinical heterogeneity between the studies. In addition to NPPV, all patients in the NPPV group also received UMC. Usual medical care varied between the studies, but common medications included supplemental oxygen, bronchodilators, corticosteroids, antibiotics, diuretics, and respiratory stimulators.
The individual quality of the studies ranged. Common methodological issues included lack of blinding and allocation concealment, and small sample sizes.
Need for Endotracheal Intubation
Eleven studies reported the need for endotracheal intubation as an outcome. The pooled results showed a significant reduction in the need for endotracheal intubation in the NPPV plus UMC group compared with the UMC alone group (relative risk [RR], 0.38; 95% confidence interval [CI], 0.28−0.50). When subgrouped by severity of respiratory failure, the results remained significant for the mild, severe, and very severe respiratory failure groups.
GRADE: moderate
Inhospital Mortality
Nine studies reported inhospital mortality as an outcome. The pooled results showed a significant reduction in inhospital mortality in the NPPV plus UMC group compared with the UMC group (RR, 0.53; 95% CI, 0.35−0.81). When subgrouped by severity of respiratory failure, the results remained significant for the moderate and severe respiratory failure groups.
GRADE: moderate
Hospital Length of Stay
Eleven studies reported hospital length of stay (LOS) as an outcome. The pooled results showed a significant decrease in the mean length of stay for the NPPV plus UMC group compared with the UMC alone group (weighted mean difference [WMD], −2.68 days; 95% CI, −4.41 to −0.94 days). When subgrouped by severity of respiratory failure, the results remained significant for the mild, severe, and very severe respiratory failure groups.
GRADE: moderate
Five studies reported complications. Common complications in the NPPV plus UMC group included pneumonia, gastrointestinal disorders or bleeds, skin abrasions, eye irritation, gastric insufflation, and sepsis. Similar complications were observed in the UMC group including pneumonia, sepsis, gastrointestinal disorders or bleeds, pneumothorax, and complicated endotracheal intubations. Many of the more serious complications in both groups occurred in those patients who required endotracheal intubation. Three of the studies compared complications in the NPPV plus UMC and UMC groups. While the data could not be pooled, overall, the NPPV plus UMC group experienced fewer complications than the UMC group.
GRADE: low
Eight studies reported patient tolerance or compliance with NPPV as an outcome. NPPV intolerance ranged from 5% to 29%. NPPV tolerance was generally higher for patients with more severe respiratory failure. Compliance with the NPPV protocol was reported by 2 studies, which showed compliance decreases over time, even over short periods such as 3 days.
NPPV Versus IMV for the Treatment of Patients Who Failed Usual Medical Care
A total of 205 participants were included in 2 studies; the sample sizes of these studies were 49 and 156. The mean age of the patients was 71 to 73 years of age in 1 study, and the median age was 54 to 58 years of age in the second study. Based on either the GOLD COPD stage criteria or the mean percent predicted FEV1, patients in 1 study had very severe COPD. The COPD severity could not be classified in the second study. Both studies had study populations with a mean pH less than 7.23, which was classified as very severe respiratory failure in this analysis. One study enrolled patients with ARF due to acute exacerbations of COPD who had failed medical therapy. The patient population was not clearly defined in the second study, and it was not clear whether they had to have failed medical therapy before entry into the study.
Both studies were conducted in the ICU. Patients in the NPPV group received BiPAP ventilatory support through nasal or full facial masks. Patients in the IMV group received pressure support ventilation.
Common methodological issues included small sample size, lack of blinding, and unclear methods of randomization and allocation concealment. Due to the uncertainty about whether both studies included the same patient population and substantial differences in the direction and significance of the results, the results of the studies were not pooled.
Both studies reported ICU mortality. Neither study showed a significant difference in ICU mortality between the NPPV and IMV groups, but 1 study showed a higher mortality rate in the NPPV group (21.7% vs. 11.5%) while the other study showed a lower mortality rate in the NPPV group (5.1% vs. 6.4%). One study reported 1-year mortality and showed a nonsignificant reduction in mortality in the NPPV group compared with the IMV group (26.1% vs. 46.1%).
GRADE: low to very low
Intensive Care Unit Length of Stay
Both studies reported LOS in the ICU. The results were inconsistent. One study showed a statistically significant shorter LOS in the NPPV group compared with the IMV group (5 ± 1.35 days vs. 9.29 ± 3 days; P < 0.001); whereas, the other study showed a nonsignificantly longer LOS in the NPPV group compared with the IMV group (22 ± 19 days vs. 21 ± 20 days; P = 0.86).
GRADE: very low
Duration of Mechanical Ventilation
Both studies reported the duration of mechanical ventilation (including both invasive and noninvasive ventilation). The results were inconsistent. One study showed a statistically significant shorter duration of mechanical ventilation in the NPPV group compared with the IMV group (3.92 ± 1.08 days vs. 7.17 ± 2.22 days; P < 0.001); whereas, the other study showed a nonsignificantly longer duration of mechanical ventilation in the NPPV group compared with the IMV group (16 ± 19 days vs. 15 ± 21 days; P = 0.86). GRADE: very low
Both studies reported ventilator-associated pneumonia and tracheotomies. Both showed a reduction in ventilator-associated pneumonia in the NPPV group compared with the IMV group, but the results were only significant in 1 study (13% vs. 34.6%, P = 0.07; and 6.4% vs. 37.2%, P < 0.001, respectively). Similarly, both studies showed a reduction in tracheotomies in the NPPV group compared with the IMV group, but the results were only significant in 1 study (13% vs. 23.1%, P = 0.29; and 6.4% vs. 34.6%; P < 0.001).
GRADE: very low
Other Outcomes
One of the studies followed patients for 12 months. At the end of follow-up, patients in the NPPV group had a significantly lower rate of needing de novo oxygen supplementation at home. In addition, the IMV group experienced significant increases in functional limitations due to COPD, while no increase was seen in the NPPV group. Finally, no significant differences were observed for hospital readmissions, ICU readmissions, and patients with an open tracheotomy, between the NPPV and IMV groups.
NPPV for Weaning COPD Patients From IMV
A total of 80 participants were included in the 2 RCTs; the sample sizes of the studies were 30 and 50 patients. The mean age of the participants ranged from 58 to 69 years of age. Based on either the GOLD COPD stage criteria or the mean percent predicted FEV1, both studies included patients with very severe COPD. Both studies also included patients with very severe respiratory failure (mean pH of the study populations was less than 7.23). Chronic obstructive pulmonary disease patients receiving IMV were enrolled in the study if they failed a T-piece weaning trial (spontaneous breathing test), so they could not be directly extubated from IMV.
Both studies were conducted in the ICU. Patients in the NPPV group received weaning using either BiPAP or pressure support ventilation NPPV through a face mask, and patients in the IMV weaning group received pressure support ventilation. In both cases, weaning was achieved by tapering the ventilation level.
The individual quality of the studies ranged. Common methodological problems included unclear randomization methods and allocation concealment, lack of blinding, and small sample size.
Both studies reported mortality as an outcome. The pooled results showed a significant reduction in ICU mortality in the NPPV group compared with the IMV group (RR, 0.47; 95% CI, 0.23−0.97; P = 0.04).
GRADE: moderate
Intensive Care Unit Length of Stay
Both studies reported ICU LOS as an outcome. The pooled results showed a nonsignificant reduction in ICU LOS in the NPPV group compared with the IMV group (WMD, −5.21 days; 95% CI, −11.60 to 1.18 days).
GRADE: low
Duration of Mechanical Ventilation
Both studies reported duration of mechanical ventilation (including both invasive and noninvasive ventilation) as an outcome. The pooled results showed a nonsignificant reduction in duration of mechanical ventilation (WMD, −3.55 days; 95% CI, −8.55 to 1.44 days).
GRADE: low
Nosocomial Pneumonia
Both studies reported nosocominal pneumonia as an outcome. The pooled results showed a significant reduction in nosocomial pneumonia in the NPPV group compared with the IMV group (RR, 0.14; 95% CI, 0.03−0.71; P = 0.02).
GRADE: moderate
Weaning Failure
One study reported a significant reduction in weaning failure in the NPPV group compared with the IMV group, but the results were not reported in the publication. In this study, 1 of 25 patients in the NPPV group and 2 of 25 patients in the IMV group could not be weaned after 60 days in the ICU.
NPPV After Extubation of COPD Patients From IMV
The literature was reviewed to identify studies examining the effectiveness of NPPV compared with UMC in preventing recurrence of ARF after extubation from IMV or treating acute ARF which has recurred after extubation from IMV. No studies that included only COPD patients or reported results for COPD patients separately were identified for the prevention of ARF postextubation.
One study was identified for the treatment of ARF in COPD patients that recurred within 48 hours of extubation from IMV. This study included 221 patients, of whom 23 had COPD. A post hoc subgroup analysis was conducted examining the rate of reintubation in the COPD patients only. A nonsignificant reduction in the rate of reintubation was observed in the NPPV group compared with the UMC group (7 of 14 patients vs. 6 of 9 patients, P = 0.67). GRADE: low
NPPV Plus UMC Versus UMC Alone for First Line Treatment of ARF due to Acute Exacerbations of COPD
Moderate quality of evidence showed that compared with UMC, NPPV plus UMC significantly reduced the need for endotracheal intubation, inhospital mortality, and the mean length of hospital stay.
Low quality of evidence showed a lower rate of complications in the NPPV plus UMC group compared with the UMC group.
NPPV Versus IMV for the Treatment of ARF in Patients Who Have Failed UMC
Due to inconsistent and low to very low quality of evidence, there was insufficient evidence to draw conclusions on the comparison of NPPV versus IMV for patients who failed UMC.
NPPV for Weaning COPD Patients From IMV
Moderate quality of evidence showed that weaning COPD patients from IMV using NPPV results in significant reductions in mortality, nosocomial pneumonia, and weaning failure compared with weaning with IMV.
Low quality of evidence showed a nonsignificant reduction in the mean LOS and mean duration of mechanical ventilation in the NPPV group compared with the IMV group.
NPPV for the Treatment of ARF in COPD Patients After Extubation From IMV
Low quality of evidence showed a nonsignificant reduction in the rate of reintubation in the NPPV group compared with the UMC group; however, there was inadequate evidence to draw conclusions on the effectiveness of NPPV for the treatment of ARF in COPD patients after extubation from IMV
PMCID: PMC3384377  PMID: 23074436
2.  Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients 
AIM: To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.
METHODS: We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008. We investigated patients who had shown acute renal failure (ARF), and examined their clinical characteristics, laboratory data, use of preventive measures, treatment cycles, the amount of cisplatin administered, recovery period, subsequent treatments, and renal status between the recovered and unrecovered groups.
RESULTS: Forty-one of the 552 patients had serum creatinine (SCR) levels greater than 1.5 mg/dL. We found that pre-ARF SCR, ARF SCR, and ARF glomerular filtration rates were significantly associated with renal status post-ARF between the two groups (P = 0.008, 0.026, 0.026, respectively). On the receiver operating characteristic curve of these values, a 1.75 mg/dL ARF SCR value had 87.5% sensitivity and 84.8% specificity (P = 0.011).
CONCLUSION: Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.
PMCID: PMC3163249  PMID: 21941418
Acute renal failure; Cisplatin; Drug toxicities; Nephrotoxicity
3.  Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review 
Noninvasive positive pressure ventilation (NPPV) refers to the delivery of mechanical respiratory support without the use of endotracheal intubation (ETI). The present review focused on the effectiveness of NPPV in children > 1 month of age with acute respiratory failure (ARF) due to different conditions. ARF is the most common cause of cardiac arrest in children. Therefore, prompt recognition and treatment of pediatric patients with pending respiratory failure can be lifesaving. Mechanical respiratory support is a critical intervention in many cases of ARF. In recent years, NPPV has been proposed as a valuable alternative to invasive mechanical ventilation (IMV) in this acute setting. Recent physiological studies have demonstrated beneficial effects of NPPV in children with ARF. Several pediatric clinical studies, the majority of which were noncontrolled or case series and of small size, have suggested the effectiveness of NPPV in the treatment of ARF due to acute airway (upper or lower) obstruction or certain primary parenchymal lung disease, and in specific circumstances, such as postoperative or postextubation ARF, immunocompromised patients with ARF, or as a means to facilitate extubation. NPPV was well tolerated with rare major complications and was associated with improved gas exchange, decreased work of breathing, and ETI avoidance in 22-100% of patients. High FiO2 needs or high PaCO2 level on admission or within the first hours after starting NPPV appeared to be the best independent predictive factors for the NPPV failure in children with ARF. However, many important issues, such as the identification of the patient, the right time for NPPV application, and the appropriate setting, are still lacking. Further randomized, controlled trials that address these issues in children with ARF are recommended.
PMCID: PMC3224494  PMID: 21906346
4.  Noninvasive positive pressure ventilation in acute respiratory failure due to COPD vs other causes: Effectiveness and predictors of failure in a respiratory ICU in North India 
To determine the effectiveness of noninvasive positive pressure ventilation (NIPPV), and the factors predicting failure of NIPPV in acute respiratory failure (ARF) due to chronic obstructive pulmonary disease (COPD) versus other causes of ARF.
Patients and methods
This was a prospective observational study and all patients with ARF requiring NIPPV over a one-and-a-half year period were enrolled in the study. We recorded the etiology of ARF and prospectively collected the data for heart rate, respiratory rate, arterial blood gases (pH, partial pressure of oxygen in the arterial blood [PaO2], partial pressure of carbon dioxide in arterial blood [PaCO2]) at baseline, one and four hours. The patients were further classified into two groups based on the etiology of ARF as COPD–ARF and ARF due to other causes. The primary outcome was the need for endotracheal intubation during the intensive care unit (ICU) stay.
During the study period, 248 patients were admitted in the ICU and of these 63 (25.4%; 24, COPD–ARF, 39, ARF due to other causes; 40 male and 23 female patients; mean [standard deviation] age of 45.7 [16.6] years) patients were initiated on NIPPV. Patients with ARF secondary to COPD were older, had higher APACHE II scores, lower respiratory rates, levels compared to other causes of ARF. After one hour there was lower pH and higher PaCO2 levels with increase a significant decrease in respiratory rate and heart rate and decline in PaCO2 levels in patients successfully managed with NIPPV. However, there was no in pH and PaO2 difference in improvement of clinical and blood gas parameters between the two groups except at one hour which was significantly the rate of decline of pH at one and four hours and PaCO2 faster in the COPD group. NIPPV failures were significantly higher in ARF due to other causes (15/39) than in ARF–COPD (3/24) (p = 0.03). The mean ICU and hospital stay and the hospital mortality were similar in the two groups. In the multivariate logistic regression model (after and adjusting for gender, APACHE II scores and improvement in respiratory rate, pH, PaO2 at one hour) only the etiology of ARF, ie, ARF–COPD, was associated with a decreased PaCO2 risk of NIPPV failure (odds ratio 0.23; 95% confidence interval, 0.58–0.9).
NIPPV is more effective in preventing endotracheal intubation in ARF due to COPD than other causes, and the etiology of ARF is an important predictor of NIPPV failure.
PMCID: PMC2650588  PMID: 19281088
noninvasive ventilation; noninvasive positive pressure ventilation; acute respiratory failure; chronic obstructive pulmonary disease; CPAP; bilevel positive airway pressure; pneumonia; ALI; ARDS
5.  Neurodiagnostic Abnormalities in Patients with Acute Renal Failure 
Journal of Clinical Investigation  1978;61(6):1448-1455.
Neurological abnormalities are a major cause of morbidity in patients with renal failure. The pathophysiology of these neurological changes is unclear, and the effects on them of dialysis and return of renal function have not been well studied. Studies were done in 31 patients who had acute renal failure (ARF), all of whom were either treated with dialysis within 5 days or did not survive. Studies on these patients included the electroencephalogram (EEG), motor nerve conduction velocity, and plasma Ca++ and parathyroid hormone (PTH) levels. Studies were done at the time ARF was diagnosed, after stabilization on dialysis, during the diuretic phase of ARF, and 3 mo after recovery from ARF. In 16 patients with acute or chronic renal failure who did not survive and in nine patients without renal disease who died, measurements were made in brain of content of Na+, K+, Cl−, Ca++, Mg++, and water.
In patients with ARF for less than 48 h, despite the fact that there were only modest increases in plasma urea and creatinine, there were striking abnormalities in the EEG. The percent EEG power < 5 Hz±SE was 41±8% (normal = 2±1%), whereas the percent of frequencies > 9 Hz was only 22±6% (normal = 62±3%). These changes were unaffected by dialysis, but became normal with return of renal function and remained normal at 3 mo follow-up. The motor nerve conduction velocity was unaffected by either ARF or dialysis. In patients with ARF, the brain Ca++ was 46.5±3.2 meq/kg dry wt, almost twice the normal value of 26.9±1.0 meq/kg dry wt (P < 0.001). The plasma PTH level was 3.2±0.6 ng/ml (normal < 1.5 ng/ml, P < 0.01). The increased brain Ca++ was not related to an increased plasma (Ca++) (PO4−−−) product (r2 = 0.14, P > 0.05). There was a small but significant decrement in brain Na+ (P < 0.05), but brain water, K+, and Mg++ were unaffected by ARF.
Thus, in patients with ARF for less than 48 h, the EEG is grossly abnormal and there are elevated levels of PTH in plasma. The PTH appears to have a direct effect on the brain, resulting in an increased brain Ca++ content. The EEG abnormalities are unaffected by dialysis, but they become normal with return of renal function and remain normal after 3 mo follow-up. Thus, PTH may be a major uremic toxin, demonstrating evidence for central nervous system toxicity when there are only minimal abnormalities of other biochemical markers of ARF.
PMCID: PMC372670  PMID: 659607
6.  Risk Factors for Renal Failure in Pediatric Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study 
Pediatric blood & cancer  2010;55(4):655-661.
In children receiving treatment for acute myeloid leukemia (AML) there is often concern for the development of acute renal failure (ARF). Despite this, data are limited to define the incidence of ARF in this population. This study aims to evaluate the rate of ARF in AML patients and to delineate the impact of age, race, various co-morbid conditions and antimicrobial agents on the development of ARF.
A cohort of newly diagnosed AML patients from children's hospitals across the United States was identified using the Pediatric Health Information Systems database. Information regarding demographics, discharge diagnoses, pharmaceutical exposures, and hospital resource utilization were collected for each hospitalization for up to 1 year from AML diagnosis. Cox regression analysis was used to define the hazard ratios for development of ARF by demographic variables, co-morbid conditions, and exposure to various antimicrobial agents.
Within 1 year of AML diagnosis, 135 (16.2%) patients were diagnosed with ARF. After adjustment for the presence of co-morbid conditions, the risk for ARF was greater in older patients and in black patients. Vancomycin exposure duration of greater than 48 hr and carbapenem exposure duration greater than 10 days were associated with an increased risk for ARF.
ARF is a relatively common problem in children with AML. Future studies should address the different risks of ARF by age and race. Empiric therapy with potentially nephrotoxic agents did not increase the risk of nephrotoxicity. Patients on prolonged vancomycin therapy should be monitored closely for development of ARF.
PMCID: PMC3909928  PMID: 20533519
antimicrobials; epidemiology; leukemia; pediatrics; renal failure
7.  Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis 
Respiratory Research  2014;15(1):27.
Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.
This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.
Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).
The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.
PMCID: PMC4015148  PMID: 24593040
Pneumonia; Sepsis; Severe sepsis; Acute respiratory failure; ARDS; CAP; Community-acquired pneumonia; Mortality; Oxygenation
8.  Evaluating the relative frequency and predicting factors of acute renal failure following coronary artery bypass grafting 
ARYA Atherosclerosis  2013;9(5):287-292.
Renal dysfunction or acute renal failure in patients undergoing coronary artery bypass grafting (CABG) is an important cause of morbidity and mortality. The great impact of acute renal failure (ARF) in the outcomes of cardiac surgery demands its study in our population, encouraging to the elaboration of this study, which aimed to identify the incidence and risk factors of ARF after CABG.
Since March 2010 to 2011, 589 patients were studied who underwent CABG in Sina Hospital (Isfahan, Iran). In this cross-sectional study, patients were divided into two groups based on the occurrence of ARF after CABG and measured variables were compared between the two groups was also statistically significant. P value less than 0.05 was set as a significant level.
A total of 434 men and 155 women were enrolled in the study. The mean age of the study subjects was 57.6 years. ARF was seen in about 22% of patients after CABG. The mean age of ARF group was more than 3 years higher than that in the other group and the difference was significant between the two groups. Serum creatinine level after the surgery was different between the two groups. Moreover, the history of diabetes mellitus was significantly different between the two groups. Pump time comparison also showed was also statistically significant.
Our data showed older patients were more prone to affected by ARF. In addition, diabetic patients should be considered as high risk patients and are more likely to deteriorate by ARF. Despite increased prevalence of renal insufficiency in CABG patients, studies show that in most cases, this is not a serious problem and it is easily treatable. A lower proportion of patients (1.0 to 1.7% in different large series) develop ARF severe enough to require dialysis.
PMCID: PMC3845695  PMID: 24302937
Coronary Artery Bypass; Acute Kidney Injury; Creatinine
9.  Utility of Serum Creatinine, Creatine Kinase and Urinary Myoglobin in Detecting Acute Renal Failure due to Rhabdomyolysis in Trauma and Electrical Burns Patients 
The Indian Journal of Surgery  2012;75(1):17-21.
Rhabdomyolysis due to trauma and burns is an important cause of acute renal failure (ARF) secondary to myoglobinuria. To prevent morbidity and mortality from ARF due to rhabdomyolysis, early detection of ARF by monitoring the biochemical parameters such as serum creatinine, serum creatine kinase (CK), and urinary myoglobin (UM) can be helpful. The aims of the study were (1) to detect ARF due to rhabdomyolysis using serum creatinine, serum CK, and UM in trauma and electrical burn patients (2) to compare utility of these parameters in early prediction of ARF in patients of rhabdomyolysis. A total of 50 patients with trauma and electrical burns were included in the study. Serum creatinine, serum CK, and UM measurements were done at the time of admission and after 48 h. Diagnosis of ARF was made in the patients by Rifle’s criteria. The presence of significant elevation of creatinine, serum CK, and UM at the time of admission and after 48 h was compared in patients developing ARF by Fisher’s exact test. Fifteen of the 50 patients developed ARF as per the defined criteria. Of these, 9 patients (60 %) had raised level of serum creatinine above 1.4 mg% at admission and 14 patients (93.33 %) had CK level >1250 U/L at admission, whereas UM was positive in 6 (40 %) patients. Serum creatinine was significantly raised in all of the 15 ARF patients (100 %) after 48 h of admission and serum CK was raised in 14 of the 15 ARF patients (93.33 %). UM was negative in all the patients after 48 h of admission. Statistical analysis showed that rise in serum CK on admission was significantly increased in patients developing ARF as compared with serum creatinine and UM (P < 0.0001). On admission, CK is a better predictor of ARF due to rhabdomyolysis than creatinine and UM. Initial creatinine is a better predictor of ARF due to rhabdomyolysis than UM. UM assay is not a good investigation for early prediction of ARF in rhabdomyolysis.
PMCID: PMC3585542  PMID: 24426377
Creatine kinase; Urinary myoglobin; Serum creatinine; Acute renal failure; Rhabdomyolysis
10.  Using continuous renal replacement therapy to manage patients of shock and acute renal failure 
The incidence of acute renal failure (ARF) in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT).
Patients and Methods:
Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration) in the intensive care unit. For the purpose of this study, shock was defined as systolic BP < 100 mm Hg in spite of administration of one or more inotropic agents. SOFA (Sequential Organ Failure Assessment) score before initiation of dialysis support was recorded in all cases. CVVHDF was performed using the Diapact® (Braun) CRRT machine. The vascular access used was as follows: femoral in 32, internal jugular in 8, arteriovenous fistula (AVF) in 4, and subclavian in 6 patients. We used 0.9% or 0.45% (half-normal) saline as a prefilter replacement, with addition of 10% calcium gluconate, magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients.
Of the 50 patients studied, 29 were males and 21 females (1.4:1). The average age was 52.88 years (range: 20–75 years). Causes of ARF included sepsis in 24 (48%), hemodynamically mediated renal failure (HMRF) in 18 (36%), and acute over chronic kidney disease in 8 (16%) patients. The overall mortality was 74%. The average SOFA score was 14.31. The variables influencing mortality on multivariate analysis were: age [odds ratio (OR):1.65; 95% CI: 1.35 to 1.92; P = 0.04], serum creatinine (OR:1.68; 95% CI: 1.44 to 1.86; P = 0.03), and serum bicarbonate (OR: 0.76; 95% CI: 0.55 to 0.94; P = 0.01). On univariate analysis the SOFA score was found to be a useful predictor of mortality.
Despite advances in treating critically ill patients with newer extracorporeal therapies, mortality is dismally high. Multiorgan dysfunction adversely affects outcome of CRRT. Older age, level of azotemia, and severity of metabolic acidosis are important predictors of adverse outcome.
PMCID: PMC2700581  PMID: 19561951
Acute renal failure; continuous renal replacement therapy; shock; sepsis
11.  Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study 
Critical Care  2005;9(6):R700-R709.
Severe acute renal failure (sARF) is associated with considerable morbidity, mortality and use of healthcare resources; however, its precise epidemiology and long-term outcomes have not been well described in a non-specified population.
Population-based surveillance was conducted among all adult residents of the Calgary Health Region (population 1 million) admitted to multidisciplinary and cardiovascular surgical intensive care units between May 1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year was assessed.
sARF occurred in 240 patients (11.0 per 100,000 population/year). Rates were highest in males and older patients (≥65 years of age). Risk factors for development of sARF included previous heart disease, stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease, chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per 100,000 population with rates highest in males and those ≥65 years. The 28-day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively. Increased Charlson co-morbidity index, presence of liver disease, higher APACHE II score, septic shock, and need for continuous renal replacement therapy were independently associated with death at 1 year. Renal recovery occurred in 78% (68/87) of survivors at 1 year.
sARF is common and males, older patients, and those with underlying medical conditions are at greatest risk. Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year.
PMCID: PMC1414056  PMID: 16280066
12.  Importance of Neutrophil Gelatinase-Associated Lipocalin in Differential Diagnosis of Acute and Chronic Renal Failure 
Neutrophil Gelatinase-associated Lipocalin (NGAL) protein is easily detected in the blood and urine soon after acute renal injury. NGAL gains features of an early, sensitive and noninvasive biomarker for acute renal injury. Recent evidences suggest that its expression is also increased in CRF reflecting the severity of disease.
In the present study, we aimed to investigate whether blood NGAL level plays a role in the differential diagnosis of acute and chronic renal failure.
Patients and Methods:
This was a prospective case-control study. Fifty patients presented to emergency department with acute renal failure (ARF), 30 with chronic renal failure (CRF) and 20 healthy individuals as control group were included in this study. Blood pH, HCO3-, BUN, creatinine and potassium values were evaluated in all patients. Blood NGAL values were evaluated in all groups. BUN, serum creatinine and NGAL values were statistically compared between patients and controls.
Median NGAL levels in patients was 304.50 (29), and 60 (0) in control, which was statistically significant between the two groups (Z = -6.477, P < 0.001). The median NGAL values were 261.50 ± 291 in ARF group and 428.50 ± 294 in CRF group. There was a significant difference in NGAL level between ARF and CRF groups (Z = -2.52, P = 0.012). Median BUN values were 153.46 ± 82.47 in ARF group and 169.40 ± 93.94 in CRF group. There was no significant difference in BUN value between ARF and CRF groups (P > 0.05). Median creatinine values were 2.84 ± 2.95 in ARF group and 4.78 ± 4.32 in CRF group. In serum creatinine values, a significant difference was found between ARF and CRF groups (P < 0.05).
Serum NGAL levels of ARF and CRF patients were significantly higher than healthy individuals. In addition, NGAL values of patients with CRF were significantly higher than those of ARF. Serum NGAL values can be used to detect renal injury and differentiate ARF and CRF.
PMCID: PMC4222006  PMID: 25389480
Renal Failure; Chronic; Acute; NGAL Protein
13.  Year in review: Critical Care 2004 – nephrology 
Critical Care  2005;9(5):523-527.
We summarize all original research in the field of critical care nephrology published in 2004 or accepted for publication in Critical Care and, when considered relevant or directly linked to this research, in other journals. Articles were grouped into four categories to facilitate a rapid overview. First, regarding the definition of acute renal failure (ARF), the RIFLE criteria (risk, injury, failure, loss, ESKD [end-stage kidney disease]) for diagnosis of ARF were defined by the Acute Dialysis Quality Initiative workgroup and applied in clinical practice by some authors. The second category is acid–base disorders in ARF; the Stewart–Figge quantitative approach to acidosis in critically ill patients has been utilized by two groups of researchers, with similar results but different conclusions. In the third category – blood markers during ARF – cystatin C as an early marker of ARF and procalcitonin as a sepsis marker during continuous venovenous haemofiltration were examined. Finally, in the extracorporeal treatment of ARF, the ability of two types of high cutoff haemofilters to influence blood levels of middle- and high-molecular-weight toxins showed promise.
PMCID: PMC1297618  PMID: 16277742
14.  Complicated falciparum Malaria in western Maharashtra 
Tropical Parasitology  2012;2(1):49-54.
Complicated falciparum malaria remains a major cause of morbidity and mortality worldwide. Plasmodium falciparum malaria is a syndrome and a disease of protean clinical manifestations. All cases of falciparum malaria are potentially severe and life threatening, especially when managed inappropriately.
The aim of the present study is to study clinical presentation and complications of patients with complicated P. falciparum malaria and its outcome.
Settings and Design:
This was retrospective observational study, conducted at tertiary care center in western Maharashtra from January 2011 to December 2011.
Materials and Methods:
Total 47 patients fulfilling criterion of complicated malaria due to P. falciparum who presented with fever having positive trophozoites of P. falciparum in blood smear were included in this study. Statistical analysis was done by EPI Info 6 statistical software.
Results and Conclusion:
A total 47 patients had smear positive complicated P. falciparum malaria with 39 were male and 8 were female patients. Total three (6.38%) patients had hypoglycemia at the time of admission. Total 29 (61.70%) patients had jaundice of which 20 were with anemia. Total 22 (46.80%) had anemia of which 20 were with jaundice. Total 6 (12.76%) had cerebral malaria, 6 (12.76%) had acute renal failure (ARF), 5 (10.63%) had acute respiratory distress syndrome (ARDS) and 1 (2.12%) had thrombocytopenia. Total 26 patients had single complication in the form of cerebral malaria 6 (12.76%), jaundice 9 (19.14%), ARF 5 (10.63%), ARDS 4 (8.51%) and anemia 2 (4.25%). Total 20 patients had two complications in the form of jaundice with anemia 20 (42.55%). One (2.12%) patient had four complications in the form of cerebral malaria with ARF with ARDS with thrombocytopenia with 100% mortality. Overall case fatality rate was 10.63% (5/47). The case fatality rate for isolated ARDS was 50% (2/4), with ARF was 20% (1/5) and with cerebral malaria it was 16.66% (1/6). Case fatality rate was highest in patients with ARDS compared to ARF and cerebral malaria with ‘P’ = 0.0221.
In present study most common presentation was jaundice and anemia. Cerebral malaria, ARF and ARDS were uncommon presentation. Overall case fatality rate of complicated P. falciparum malaria was 10.63%. The case fatality rate was highest with multi-organ dysfunction (100%). This study highlights the significant burden of P. falciparum complicated malaria with isolated complication like ARDS with high mortality rate of 50% in present population.
PMCID: PMC3593511  PMID: 23507667
Complicated falciparum malaria; acute respiratory distress syndrome; acute renal failure; multi-organ dysfunction; cerebral malaria
15.  Acute renal failure mortality in hospitalized African Americans: age and gender considerations. 
The aging kidney is at risk for both toxic and hemodynamic-induced acute damage, resulting in a high incidence of acute renal failure (ARF) in elderly patients. The effect of age and or gender in ARF mortality in African Americans (AA) was studied in a 3-year, computer assisted retrospective review. In an inner city medical center, 100 patients classified as ARF at discharge or expiration were included in the study. Patients were classified into 3 age categories: <40, 40-64, and >64 years. The incidence of ARF was 35%, 28% and 37%, respectively. Patients >64 years of age were less likely to be dialyzed. Both pre- and postrenal causes of ARF were more common in patients >64 years of age than in younger patients. Hospital length of stay increased progressively with age. Mortality was lower in patients >64 years of age than in younger patients. The incidence of ARF was higher in male than female patients and the incidence of sepsis was higher in female than male patients. Dialytic need was greater in male patients, but mortality was higher in female than male patients. Multivariate logistic regression showed that in the presence of sepsis, oliguria and mechanical ventilatory support, the relative risk of mortality associated with advanced age was 16.5, the relative risk of mortality associated with female gender was 0.2. In summary, hospitalized elderly African-American patients have a high incidence of ARF, and patients less than 40 years of age are equally at risk. Although mortality was higher in female patients, gender and advanced age did not independently contribute to high mortality. Neither age nor gender considerations should supplant sound clinical judgment in the management of and decision making in elderly African-American patients with ARF.
PMCID: PMC2594093  PMID: 11918381
16.  Muscle protein turnover and glucose uptake in acutely uremic rats. Effects of insulin and the duration of renal insufficiency. 
Journal of Clinical Investigation  1983;72(3):836-845.
Acute renal failure (ARF) in rats is associated with increased amino acid release from peripheral tissues and insulin resistance. To study whether abnormal protein and carbohydrate metabolism are linked in ARF, the effects of insulin on net muscle protein degradation (T) and on glucose uptake were measured in the perfused hindquarters of paired ARF and sham-operated (SO) rats. The basal rate of T increased 40% after 24 and 98% after 48 h of ARF. Insulin was less effective in decreasing T in ARF (-79% SO vs. -22% ARF 24 h and -64% SO vs. -23% ARF 48 h; P less than 0.01). Protein synthesis (PS) and protein degradation (PD) were measured independently in incubated epitrochlearis muscles; the increase in T after 24 h of ARF was due specifically to increased PD, while PS was unchanged. At this stage, insulin was less effective in decreasing PD in ARF (-10% ARF vs. -23% SO; P less than 0.02), although PS responded normally. After 48 h of ARF, the further increment in T was caused by the additional appearance of depressed basal and insulin-stimulated PS. This was confirmed in the perfused hindquarter (26 +/- 3 ARF vs. 38 +/- 3 SO, basal; 54 +/- 5 ARF vs 73 +/- 7 SO, insulin-stimulated, nmol phenylalanine/g per h; P less than 0.05). Although basal glucose uptake by hindquarters of ARF and SO rats was comparable, insulin-stimulated glucose uptake was 33% less at 24 and 44% less after 48 h of ARF. After 48 h of ARF, lactate and alanine release were increased and net glycogen synthesis in muscle was depressed. These abnormalities were even more apparent in the presence of insulin. Inefficient glucose utilization, estimated as the ratio of lactate release to glucose uptake, was correlated with T (r = +0.78; P less than 0.001). In conclusion, after 24 h of ARF, both increased PD and altered glucose utilization could be detected. After 48 h of ARF, T increased further because PS was depressed. At this time, glucose utilization was clearly abnormal and the results suggest that abnormal net protein degradation in ARF may be a consequence of defective glucose utilization.
PMCID: PMC1129248  PMID: 6350366
17.  A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy 
BMC Nephrology  2012;13:96.
Because of the rapid growth in elderly population, polypharmacy has become a serious public health issue worldwide. Although acute renal failure (ARF) is one negative consequence of polypharmacy, the association between the duration of polypharmacy and ARF remains unclear. We therefore assessed this association using a population-based database.
Data were collected from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 through 2006. The case group included patients hospitalized for ARF during 2006, but not admitted due to trauma, surgery, burn trauma, car accident, transplantation, or infectious diseases; the control group included patients hospitalized without ARF. The cumulative number of days of polypharmacy (defined as more than 5 prescriptions per day) for 1 year prior to admission was determined, with patients further subdivided into 4 categories: less than 30 days, 31–90 days, 91–180 days, and over 181 days. The dependent variable was ARF, and the control variables were age, gender, comorbidities in patients hospitalized for ARF, stay in ICUs during ARF hospitalization and site of operation for prior admissions within one month of ARF hospitalization.
Of 20,790 patients who were admitted to hospitals for ARF in 2006, 12,314 (59.23 %) were male and more than 60 % were older than 65 years. Of patients with and without ARF, 16.14 % and 10.61 %, respectively, received polypharmacy for 91–180 days and 50.22 % and 24.12 %, respectively, for over 181 days. A statistical model indicated that, relative to patients who received polypharmacy for less than 30 days, those who received polypharmacy for 31–90, 91–180 and over 181 days had odds ratios of developing ARF of 1.33 (p<0.001), 1.65 (p<0.001) and 1.74 (p<0.001), respectively.
We observed statistically significant associations between the duration of polypharmacy and the occurrence of ARF.
PMCID: PMC3447669  PMID: 22935542
18.  Survey of acute renal failure in patients with cystic fibrosis in the UK 
Thorax  2007;62(6):541-545.
There has been a recent increase in the number of reported cases of acute renal failure (ARF) in cystic fibrosis (CF). A study was undertaken to determine the incidence risk of ARF in patients with CF in the UK and to identify possible aetiological factors.
All doctors working at UK CF centres were asked if they had been involved with the management of a patient with CF who had developed ARF. Those responding positively were asked to request informed consent for entry into the study and the patient's case notes were then reviewed. The analysis was restricted to patients developing ARF between 1997 and 2004. A second questionnaire sought information on aminoglycoside prescribing practice.
Responses were received from 55 of 56 centres with 64 reports, 9 of which were duplicates, leaving 55 cases. Consent was obtained for data extraction in 26 cases, of which 24 fitted the criteria for ARF (verified data). Median age at presentation with ARF was 9.7 years (range 0.4–31.8) and 12 cases were male. The incidence risk of ARF was 4.6 (verified data) to 10.5 cases (all data)/10 000 CF patients/year. In 21 cases (88%) an aminoglycoside was prescribed at onset of ARF or in the preceding week; 16 (76%) of those receiving an aminoglycoside had gentamicin. A renal biopsy was performed in 7 cases and histological examination revealed acute tubular necrosis in 6, all of whom had received gentamicin. Renal dialysis was required in 13 cases (54%). Complete recovery was seen in 22/24 patients (92%).
ARF is increasingly being recognised in patients with CF. There is significant morbidity with most patients requiring dialysis. This study implicates intravenous aminoglycosides, particularly gentamicin, in the aetiology of ARF in CF.
PMCID: PMC2117213  PMID: 17234661
19.  Expression of Endothelin-1 and Its Receptors in Cisplatin-Induced Acute Renal Failure in Mice 
Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors (ETAR and ETBR) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-1 and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin-treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ETAR mRNA and protein. Most of the increased immunoreactive ET-1 and ETAR were localized in damaged tubules. Neither the expression of ETBR mRNA nor the abundance and immunoreactive level of ETBR protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.
PMCID: PMC2788629  PMID: 19967049
Cisplatin; Acute renal failure; Endothelin; Endothelin receptor
20.  Parenteral nutrition in patients with renal failure – Guidelines on Parenteral Nutrition, Chapter 17 
Partial EN (enteral nutrition) should always be aimed for in patients with renal failure that require nutritional support. Nevertheless PN (parenteral nutrition) may be necessary in renal failure in patient groups with acute or chronic renal failure (ARF or CRF) and additional acute diseases but without extracorporeal renal replacement therapy, or in patients with ARF or CRF with additional acute diseases on extracorporeal renal replacement therapy, haemodialysis therapy (HD), peritoneal dialysis (PD) or continuous renal replacement therapy (CRRT), or in patients on HD therapy with intradialytic PN. Patients with renal failure who show marked metabolic derangements and changes in nutritional requirements require the use of specifically adapted nutrient solutions. The substrate requirements of acutely ill, non-hypercatabolic patients with CRF correspond to those of patients with ARF who are not receiving any renal replacement patients therapy (utilisation of the administered nutrients has to be monitored carefully). In ARF patients and acutely ill CRF patients on renal replacement therapy, substrate requirements depend on disease severity, type and extent/frequency of extracorporeal renal replacement therapy, nutritional status, underlying disease and complications occurring during the course of the disease. Patients under HD have a higher risk of developing malnutrition. Intradialytic PN (IDPN) should be used if causes of malnutrition cannot be eliminated and other interventions fail. IDPN should only be carried out when modifiable causes of malnutrition are excluded and enhanced oral (like i.e. additional energy drinks) or enteral supply is unsuccessful or cannot be carried out.
PMCID: PMC2795369  PMID: 20049069
acute renal failure; chronic renal failure; haemodialysis; peritoneal dialysis
21.  Impaired IL-18 processing protects caspase-1–deficient mice from ischemic acute renal failure 
Journal of Clinical Investigation  2001;107(9):1145-1152.
We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1β and IL-18, were protected against ischemic acute renal failure (ARF). Caspase-1–/– mice developed less ischemic ARF as judged by renal function and renal histology. These animals had significantly reduced blood urea nitrogen and serum creatinine levels and a lower morphological tubular necrosis score than did wild-type mice with ischemic ARF. Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1–/– mice from ARF. In wild-type animals, we found that ARF causes kidney IL-18 levels to more than double and induces the conversion of the IL-18 precursor to the mature form. This conversion is not observed in caspase-1–/– ARF mice or sham-operated controls. We then injected wild-type mice with IL-18–neutralizing antiserum before the ischemic insult and found a similar degree of protection from ARF as seen in caspase-1–/– mice. In addition, we observed a fivefold increase in myeloperoxidase activity in control mice with ARF, but no such increase in caspase-1–/– or IL-18 antiserum–treated mice. Finally, we confirmed histologically that caspase-1–/– mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration.
PMCID: PMC209282  PMID: 11342578
22.  Community-based incidence of acute renal failure 
Kidney international  2007;72(2):208-212.
There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system –Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100 000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.
PMCID: PMC2673495  PMID: 17507907
acute renal failure; dialysis; epidemiology; acute kidney injury; acute dialysis; disease incidence
23.  Noninvasive positive-pressure ventilation: a utilization review of use in a teaching hospital 
The use of noninvasive positive-pressure ventilation (NIPPV) for acute respiratory failure (ARF) has become more widespread over the past decade, but its prescription, use and outcomes in the clinical setting remain uncertain. The objective of this study was to review the use of NIPPV for ARF with respect to clinical indications, physician ordering, monitoring strategies and patient outcomes.
A total of 91 consecutive adult patients admitted between June 1997 and September 1998 to a university-affiliated tertiary care hospital in Hamilton, Ont., who received 95 trials of NIPPV for ARF were included in an observational cohort study. Data abstraction forms were completed in duplicate, then relevant clinical, physiologic, prescribing, monitoring and outcome data were abstracted from the NIPPV registry and hospital records.
The most common indications for NIPPV were pulmonary edema (42 of 95 trials [44.2%]) and exacerbation of chronic obstructive pulmonary disease (23 of 95 trials [24.2%]). NIPPV was started primarily in the emergency department (62.1% of trials), however, in terms of total hours of NIPPV the most frequent sites of administration were the intensive care unit (30.9% of total hours) and the clinical teaching unit (20.2% of total hours). NIPPV was stopped in 48.4% of patients because of improvement and in 25.6% because of deterioration necessitating endotracheal intubation. The median time to intubation was 3.0 hours (interquartile range 0.8-12.2 hours). The respirology service was consulted for 28.4% of the patients. Physician orders usually lacked details of NIPPV settings and monitoring methods. We found no significant predictors of the need for endotracheal intubation. The overall death rate was 28.6%. The only independent predictor of death was a decreased level of consciousness (odds ratio 2.9, 95% confidence interval 1.0-8.4).
NIPPV was used for ARF of diverse causes in many hospital settings and was started and managed by physicians with various levels of training and experience. The use of this technique outside the critical care setting may be optimized by a multidisciplinary educational practice guidelin
PMCID: PMC80545  PMID: 11068568
24.  The kidney in pregnancy: A journey of three decades 
Indian Journal of Nephrology  2012;22(3):159-167.
The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3–5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy.
PMCID: PMC3459517  PMID: 23087548
Acute kidney injury; kidney disease; preeclampsia; pregnancy; renal cortical necrosis
25.  Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure 
Critical Care  2014;18(1):R20.
Acute respiratory failure (ARF) is the main reason for intensive care unit (ICU) admissions in patients with hematologic malignancies (HMs). We report the first series of adult patients with ARF and HMs treated with extracorporeal membrane oxygenation (ECMO).
This is a retrospective cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n = 5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10), thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and transfusion-related acute lung injury (n = 1). Diagnosis of HM was established during ECMO in four patients, and five first received (immuno-) chemotherapy on ECMO.
Before ECMO, the PaO2/FiO2 ratio was 60 (53 to 65), (3.3 to 3.7). Three patients received venoarterial ECMO because of acute circulatory failure in addition to ARF; all other patients received venovenous ECMO. All patients needed vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months); five patients were in complete remission, one in partial remission, and one had relapsed.
ECMO therapy is feasible in selected patients with HMs and ARF and can be associated with long-term disease-free survival.
PMCID: PMC4055976  PMID: 24443905

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