Ari Manuel

Obesity hypoventilation syndrome: does the current definition need revisiting?

Obesity hypoventilation syndrome (OHS) has been conventionally (and to some extent arbitrarily) defined by the combination of obesity (body mass index (BMI) >30 kg/m2), daytime hypercapnia (arterial partial pressure of carbon dioxide (PaCO2) ≥45 mm Hg or 6 kPa) during wakefulness, and usually (but not always) the presence of ‘sleep disordered breathing’, such as obstructive sleep apnoea, rapid eye movement sleep hypoventilation or both.1 The survival curve for untreated OHS is significantly reduced compared with the non-obese,2 and so early identification and treatment for these patients is likely to be beneficial. Little is currently known about the true prevalence of OHS in ambulatory obese individuals, with estimates range from 0.3–0.4% of the general population,3 to around 30% of hospitalised patients with a BMI >35 kg/m …

Role of CT in assessing pleural malignancy prior to thoracoscopy

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as ‘malignant’ in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

Biomarkers of oxidative stress following continuous positive airway pressure withdrawal: data from two randomised trials

There is conflicting evidence whether intermittent hypoxia in obstructive sleep apnoea (OSA) influences oxidative stress. We hypothesised that withdrawal of continuous positive airway pressure (CPAP) from patients with OSA would raise markers of oxidative stress. 59 patients with CPAP-treated moderate-to-severe OSA (oxygen desaturation index (ODI) >20 events·h−1) were randomised 1:1 to either stay on CPAP (n=30) or change to sham CPAP (n=29) for 2 weeks. Using samples from two similar studies at two sites, we measured early morning blood malondialdehyde (MDA, a primary outcome in one study and a secondary outcome in the other), lipid hydroperoxides, total antioxidant capacity, superoxide generation from mononuclear cells and urinary F2-isoprostane. We also measured superoxide dismutase as a marker of hypoxic preconditioning. “Treatment” effects (sham CPAP versus CPAP) were calculated via linear regression. Sham CPAP provoked moderate-to-severe OSA (mean ODI 46 events·h−1), but blood markers of oxidative stress did not change significantly (MDA “treatment” effect (95% CI) −0.02 (−0.23 to +0.19) μmol·L−1). Urinary F2-isoprostane fell significantly by ∼30% (−0.26 (−0.42 to −0.10) ng·mL−1) and superoxide dismutase increased similarly (+0.17 (+0.02 to +0.30) ng·mL−1). We found no direct evidence of increased oxidative stress in patients experiencing a return of their moderate-to-severe OSA. The fall in urinary F2-isoprostane and rise in superoxide dismutase implies that hypoxic preconditioning may have reduced oxidative stress. Obstructive sleep apnoea may induce hypoxic preconditioning and reduce, rather than increase, oxidative stress http://ow.ly/MaUoN

Correlates of obesity-related chronic ventilatory failure

Introduction Only a third of obese patients develop chronic ventilatory failure. This cross-sectional study assessed multiple factors potentially associated with chronic ventilatory failure. Materials/patients and methods Participants had a body mass index (BMI) >30 kg/m2, with or without chronic ventilatory failure (awake arterial partial pressure of carbon dioxide >6 kPa or base excess (BE) ≥2 mmols/L). Factors investigated were grouped into domains: (1) obesity measures, (2) pulmonary function, (3) respiratory and non-respiratory muscle strength, (4) sleep study derivatives, (5) hypoxic and hypercapnic responses, and (6) some hormonal, nutritional and inflammatory measures. Results 71 obese participants (52% male) were studied over 27 months, 52 (SD 9) years and BMI 47 (range 32–74) kg/m2. The best univariate correlates of BE from each domain were: (1) dual-energy X-ray absorptiometry measurement of visceral fat (r=+0.50, p=0.001); (2) supine forced expiratory volume in 1 s (r=−0.40, p=0.001); (3) sniff maximum pressure (r=−0.28, p=0.02); (4) mean overnight arterial oxygen saturation (r=−0.50, p<0.001); (5) ventilatory response to 15% O2 breathing (r=−0.28, p=0.02); and (6) vitamin D (r=−0.30, p=0.01). In multivariate analysis, only visceral fat and ventilatory response to hypoxia remained significant. Conclusions We have confirmed that in the obese, BMI is a poor correlate of chronic ventilatory failure, and the best independent correlates are visceral fat and hypoxic ventilatory response. Trial registration number NCT01380418.

The role of cardiac biomarkers for predicting left ventricular dysfunction and cardiovascular mortality in acute exacerbations of COPD.

The presence of cardiovascular comorbidities is frequently associated with poor outcomes in chronic obstructive pulmonary disease (COPD). No clear role has been defined for cardiac biomarkers in acute exacerbations of COPD (AECOPD). The aim of this systematic review was to examine the prognostic value of brain natriuretic peptide (BNP) and troponins in patients with AECOPD. Two independent authors searched the PubMed and Cochrane Library to collect clinical trials, observational studies and meta-analyses studying the prognostic value of cardiac biomarkers in AECOPD. The reference lists of all the included studies were also reviewed. A total of 14 studies were included in the review, of which 10 measured troponins, 7 measured BNP or NT-proBNP, and 3 measured both. Of the studies that used mortality in AECOPD as an end point, some but not all found that elevated BNP and/or troponins were associated with increased mortality. Of the studies that used left ventricular (LV) dysfunction in AECOPD as an end point, all found a significant association between elevated BNP and troponins in the diagnosis of LV dysfunction. In summary, it appears that there may be a link between an elevated level of BNP or NT-proBNP and increased cardiovascular mortality in AECOPD, although the data currently available are not conclusive. The inconsistencies in biomarkers measured, time points of measurements and the variability in outcome measured preclude more robust analysis.

Noninvasive ventilation: has Pandora’s box been opened?

Exacerbations of COPD are the largest single cause of hospital admission with respiratory disease, and are frequently associated with impaired gas exchange and mortality rates of up to 14%.1 Acute hypercapnic respiratory failure leads to admissions to intensive care units with a mortality rate of 59% at one year.2 Noninvasive ventilation (NIV) is a well established and validated therapy for acidotic hypercapnia respiratory failure in COPD,1 a leading cause of global mortality and morbidity. The use of NIV in patients with acute type II or chronic respiratory failure has increased over the past 10 years. A Cochrane Systematic Review determined the efficacy of NIV in the management of patients with respiratory failure due to an acute exacerbation of COPD. NIV resulted in decreased mortality, decreased need for intubation, and a reduction in treatment failure.1 However a Royal College of Physicians/British Thoracic Society (RCP/BTS) audit failed to provide evidence that NIV was effective in reducing mortality. The reason for their finding is unclear.3 There is little convincing evidence for the use of NIV in severe, but stable COPD. In many cases, patients with severe chronic COPD may not tolerate long-term NIV. However, NIV has been accepted as the convention for ventilation support for patients who have developed progressive type II respiratory failure.4 What is less clear, however, is the quality of how NIV is delivered to patients in hospitals in the UK. The RCP/BTS audit of NIV use in 233 hospitals showed NIV was available in all but 11 hospitals, but only 31% of patients who were admitted with hypercapnic acidotic exacerbations of COPD (pH < 7.35) received NIV.3 A recent update of the guidelines of NIV has reinforced much of current practice but thrown up several interesting questions.5 Data from the recent BTS National COPD audit (NCROP) demonstrated large gaps in training of staff, provision of written guidelines and the ability to audit practice.6 Any patient on NIV is classified as receiving Critical Level 2 care, defined as “Patients requiring more detailed observation or intervention including support for a single failed organ system”. This suggests NIV should be administered in an intensive care unit (ICU) or high dependency unit (HDU) setting, but it has been widely recognised that NIV can be successfully used outside the ICU or HDU. In the UK previous studies have shown that 40% of NIV is performed on general medical/respiratory wards, 12% by HDUs and 13% by ICU.2 We conducted a prospective review of NIV practice at our hospital in order to compare local practice against guideline stated best practice. In this review, conducted over one year, we noted that 64% of patients were started on NIV in the accident and emergency department. The new guidelines suggest that a dedicated area of high-dependency care is needed with appropriately trained staff. Certainly most emergency departments have this, but efforts need to be made to ensure training is adequate and that staff keeps up to date. Concerns have been raised about the use of NIV in situations other than hypercapnic respiratory failure in the context of COPD. Technological advances have made the technique relatively simple and thus we are concerned that NIV is being inappropriately used, most often in the wrong indication. This may result in serious negative clinical consequences. In our review of local practice, we found 55% of patients were receiving NIV for either heart failure or pneumonia, neither of which are indications for use of NIV in the BTS guidelines.5 In the RCP survey, of the 1095 patients who were not commenced on NIV despite fulfilling criteria, the reasons for not starting NIV included “inappropriate” in 321, “no facilities” in 48, “patient refused” in 13, “treatment failed” in 3, with no reason offered in 710.3 A review of NIV use in patients with acute cardiogenic pulmonary edema showed a significant reduction in the mortality rate by nearly 45% compared with conventional therapy. There was also a significant decrease in the “need to intubate” rate. However, continuous positive airway pressure or bilevel positive airway pressure showed no differences in intubation or mortality rates in the analysis of studies comparing the two techniques.7 The new guidelines recommend that efforts must be now made to comment on gaining the patient’s consent and document the reasoning for the use of NIV. From a patient’s perspective, more compliance would be gained if the patient felt they had some control of the process and if a variety of interfaces were tried. But in a busy emergency department, these are often not feasible. We found poor documentation on patient’s consent to treatment and also almost one in seven had no documentation of why NIV was instituted. The new guidelines also state that at least a second year speciality trainee (ST2) must make the decision on the commencement of NIV, but we found that in 25% of cases this was not the case. This is especially difficult in most emergency units as they are often staffed by a mixture of nonspecialist junior and middle-grade trainees. NIV is a very well validated and successful treatment when used for the right indication, with the correctly trained staff and with motivated patients. At present we believe that there are problems common to many emergency and respiratory departments which urgently need addressing. Solutions need to be designed and implemented by local teams. They might include a dedicated NIV team, able to provide 24/7 care. This is, however, only feasible in large units with many trained staff. For smaller units lead staff should be trained regularly to maintain knowledge and competencies for this important intervention, which is most often utilized in the period termed “out-of hours”.

Exploratory study into the effect of abdominal mass loading on airways resistance and ventilatory failure

Objective We hypothesised that the airway resistance during tidal breathing would correlate with a particular pattern of increasing obesity, particularly when supine, and would differ between participants with and without ventilatory failure. Methods In our cross-sectional cohort study, 72 morbidly obese patients (40 males, 32 females, mean body mass index (BMI) 47.2) had measurements of both airways resistance (by impulse oscillometry (IOS)) and adiposity (by dual-energy X-ray absorptiometry (DXA)). Results All measures of airways resistance increased in the supine position: total airways resistance (R5) +37% (p<0.0005); large airways resistance (R20) +29% (p<0.0005); and small airways resistance (R5–R20) +52% (p<0.0005). BMI was correlated with seated R5, seated R5–R20, supine R5 and supine R5–R20 (r=0.33 p<0.006, r=0.32 p<0.004, r=0.30 p<0.02 and r=0.36 p<0.04, respectively). Visceral adipose tissue mass was correlated with supine R5–20 (r=0.46 p<0.05). Supine measures of total airways resistance (R5) and large airways resistance (R20) differed between those with and without ventilatory failure, as did mean weight and BMI. Conclusions Our study identifies a potentially detrimental effect of the supine posture on tidal breathing airways resistance in obese patients. This change is correlated most with visceral adipose tissue mass and the small airways. We were able to demonstrate that supine increases in airways resistance during tidal breathing, within obese patients, are different between those with and without ventilatory failure. Trial registration number NCT01380418; pre-results.

Rebuttal: 'Obesity hypoventilation syndrome (OHS): does the current definition need revisiting?'.

In response to the comments by Tulaimat and Littleton,1 we will clarify our original statement on ‘Obesity hypoventilation syndrome (OHS): does the current definition need revisiting?2 The two issues that these authors raise are curious and indeed re-enforce the statement …

Drugs and Medications

Obesity is becoming one of the major health problems across the world [1]. The risks involved with being overweight or obese are related to the deposition of adipose tissue (adiposity) that is associated with increased risk of adverse health problems. Dosing medications in obese subjects is a challenge as these patients are often excluded from many premarketing clinical drug trials. Current dosage recommendations for most drugs for obese patients are most often inferred from normal-weight persons. As the pharmacokinetics (PK) and pharmacodynamics (PD) of many drugs are altered by the disproportional increase of adiposity relative to lean body mass in morbid obesity, dosing based on total body weight could lead to the risk of overdose and serious clinical complications. An individualised dosing scalar that takes into account the changed body composition should be used in MO patient, particularly in anaesthesia and intensive care.

A method for calculation of arterial blood gas values from measurements in the peripheral blood (v-TAC): The first UK study

Abstract Body Background: Arterial blood gas (ABG) sampling is an essential assessment of patient’s acid-base and blood gas status, especially in patients with chronic stable ventilatory failure; however, sample collection is complex and unpleasant. Venous blood gas (VBG), in comparison, is straight forward and is less painful for the patient. A method (named v-TAC) mathematically arterialises venous blood gas values. Our study aimed to validate this method in patients with chronic stable respiratory failure Method: Consecutive sample pairs were collected on patients in chronic stable ventilatory failure. An ABG, VBG and Pulse Oximeter were measured for each patient. An independent researcher performed the arterialisation of the venous blood gas values, blinded to the arterial blood gas result. Primary outcome was agreement between mathematically arterialised venous values and arterial values for pH, pCO 2 and pO 2 Results: Twenty five sample-pairs (25 patients) were studied. Mean difference for arterial pH (actual-calculated ) was 0.002 pH units. Mean difference for pCO 2 and PO 2 (actual-calculated) was -0.14kPa and -0.2kPa respectively. Please see Bland-Altman agreement plot analysis for results Conclusion: For patients in chronic stable ventilatory failure, agreement between mathematically arterialised venous values and arterial values was close for pH and moderate for pCO 2 and pO 2 . Further large studies are needed to confirm that v-TAC is a clinically useful tool in this group of patients