Changes in serum phosphate during treatment of diabetic ketoacidosis: predictive significance of severity of acidosis on presentation.

Changes in serum phosphate during diabetic ketoacidosis (DKA) treatment are not well characterised, although it is known that serum phosphate falls with treatment. We sought to define the nature of these changes and whether the severity of acidosis on admission influenced the severity of subsequent hypophosphataemia. We retrospectively reviewed data on all patients with confirmed DKA presenting to our unit between 2007 and 2010 inclusive. Forty-three patients with 64 episodes of DKA were evaluated. At presentation, 62.5% of patient episodes were hyperphosphataemic. Initial serum phosphate in all patient episodes correlated significantly with the initial serum creatinine (r = 0.694, P < 0.01) and the initial blood glucose (r = 0.593, P < 0.01). Serum phosphate fell during the course of treatment in all episodes (mean absolute fall 1.28 ± 0.77 (SEM) mmol/L). The mean nadir phosphate was 0.58 ± 0.19 mmol/L. Ninety per cent of nadir phosphate levels were hypophosphataemic (<0.8 mmol/L), and 11% were severely hypophosphataemic (<0.32 mmol/L). Mean initial bicarbonate differed significantly between those with nadir phosphates <0.5 mmol/L (9.26 ± 4.55) and those with nadir phosphates >0.5 mmol/L (13.0 ± 4.59, P = 0.0031). Similar significant bicarbonate differences were noted between those with nadir phosphates less than and more than 0.32 mmol/L respectively (7.42 ± 2.44 and 12.2 ± 4.87, P < 0.01). The initial hyperphosphataemia is reflective of intravascular volume depletion and pre-renal renal impairment. The severity of subsequent hypophosphataemia can be predicted by the degree of metabolic acidosis on presentation. As profound hypophosphataemia can be associated with serious complications, clinicians should recognise the likelihood of this biochemical derangement in those DKA patients presenting with profound acidosis.

Severe refractory hypoxaemia in submassive pulmonary embolism: a surrogate marker of severe right ventricular dysfunction and indication for thrombolysis.

The role of thrombolysis in pulmonary thromboembolism is controversial. We describe a case of life-threatening acute pulmonary embolism where thrombolysis was successfully administered because of extreme refractory hypoxaemia. We suggest that profound refractory hypoxaemia in this clinical setting was due to the combination of severe right ventricular dysfunction and shunting from pulmonary infarction. The shunt was not likely to have resolved in the short term, but right ventricular function and hypoxaemia improved with clot lysis. Similar clinical presentations should prompt active consideration of thrombolysis.

The oncoprotective fever hypothesis: Have antibiotics, antimalarials and antipyrectics contributed to the global rise in cancer over the past century?

The adaptive and therapeutic nature of fever has been recognized for centuries and both local and systemic thermotherapy are now used to enhance the effectiveness of both chemotherapy and radiation therapy for cancer. We propose that the success of antiseptic, antibiotic, antipyretic and antimalarial strategies and medications over the past century and a half may have had the unintended effect of releasing precancerous growths and neoplastic foci from the inhibitory effects of intermittent fever. This may be a previously unrecognized factor in the overall rise in cancer rates in the late 19th and early 20th centuries.

The vitamin D positive feedback hypothesis of inflammatory bowel diseases.

While it appears that there are a variety of factors that exacerbate IBD, it is frustrating that symptoms can persist and worsen even when environmental insults are removed. We suggest that there may be a positive feedback loop which perpetuates the inflammatory response in IBD patients. The loop is triggered by vitamin D deficiency which reduces calcium uptake. Lowered vitamin D and calcium interfere with anti-inflammatory pathways. Inflammation of the mucosa inhibits absorption of calcium and thus perpetuates the reduced anti-inflammatory response. A number of predictions follow from this hypothesis and are supported by geographic and lifestyle patterns in IBD incidence and prevalence.

Massive macroglossia as a presenting feature of hypothyroid-associated pericardial effusion.

An 81-year-old woman presented with massive macroglossia and signs of both hypothyroidism and pericardial tamponade. Drainage of the pericardial effusion produced dramatic resolution of the macroglossia. Marked elevation of central venous pressure may result in macroglossia, possibly because of anomalous venous drainage of the tongue.

Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history.

STUDY OBJECTIVE: To establish the natural history of lung injury in adult respiratory distress syndrome (ARDS) in terms of increased pulmonary vascular permeability. Secondly, to relate such changes to the number of neutrophils in bronchoalveolar lavage (BAL) and a clinical score of the severity of lung injury. DESIGN: Prospective, open. SETTING: Adult intensive care unit of a tertiary (national) referral hospital. PATIENTS: Fourteen patients meeting accepted diagnostic criteria for ARDS. INTERVENTIONS: Mechanical ventilatory support. Conventional intensive care and support for other failed organ systems as appropriate. MEASUREMENTS AND RESULTS: Pulmonary vascular permeability was estimated using a dual isotope technique (protein accumulation index [PAI]), neutrophil numbers by BAL and the severity of ARDS by the lung injury score (LIS). The PAI and LIS were measured simultaneously on three occasions as far apart as possible during the course of the illness. A single BAL was performed immediately after one of the three PAI/LIS measurements, the precise timing being dictated by the clinical stability of each patient. Fourteen patients (8 male; age range, 19 to 69 years) were studied, 1.40 +/- 0.16, 11.36 +/- 1.79, and 20.90 +/- 2.30 days after the onset of ARDS (mean +/- SEM). Six patients died. The PAI (normal range, 0 to 1.0 x 10(-3)) was 2.81 +/- 0.39, 2.94 +/- 0.48, and 2.80 +/- 0.87; and LIS (severe injury > or = 2.5) was 2.18 +/- 0.25, 2.48 +/- 0.14, and 2.06 +/- 0.27, respectively. The BAL neutrophil content was 54.09 +/- 8.89. There were significant positive correlations between PAI and LIS (r = 0.73, p < 0.001) and PAI and BAL neutrophil content (r = 0.81, p < 0.001). CONCLUSIONS: These data suggest that increased pulmonary vascular permeability persists throughout the course of ARDS and is related to a clinical score of injury severity and BAL neutrophil content.

Acute respiratory distress syndrome in a community hospital ICU.

OBJECTIVE: To estimate the incidence of the acute respiratory distress syndrome (ARDS) in an Australian urban community, and to describe the pattern of disease and outcomes in a community hospital intensive care unit (ICU). SETTING: An eight-bed general ICU in a community hospital. DESIGN: Retrospective chart review. PATIENTS: 32 patients identified over a 4-year period as having ARDS. MEASUREMENTS AND RESULTS: The incidence of ARDS in an Australian urban community was estimated to be 7.3-9.3 cases/100,000 population per year. In-hospital mortality was 59%, while ICU mortality was 47%. Sepsis, pneumonia and aspiration were the main aetiological factors accounting for 94% of the patient population. There was no trauma. The Acute Physiology and Chronic Health Evaluation and Murray scores and values for the ratio of the partial pressure of oxygen in arterial blood and fractional inspired oxygen on admission to the ICU were similar between survivors and nonsurvivors, and none of these parameters were reliable predictors of outcome. Mean age, however, was different between survivors (56 +/- 16 years) and non-survivors (69 +/- 9 years) (p < or = 0.01). Mean daily fluid balance was also different between survivors (536 +/- 545 ml/day) and non-survivors (1576 +/- 1255 ml/day) (p < or = 0.02). Haemodynamic data were collected on 21 of the 32 patients within 72 h of the onset of ARDS. None of the haemodynamic parameters reached significance. There was, however, a trend for better cardiac function and oxygen consumption in the survivors. CONCLUSIONS: These data show that for ARDS, at least, mortality outcome can be comparable in a community ICU to a tertiary referral institution. The pattern of disease in an urban Australian community hospital is different to that often reported from tertiary centres. The incidence of ARDS in an Australian urban community is comparable to the reported incidence in North America and Western Europe.

Epithelial and endothelial flux after bypass in dogs: effect of positive end-expiratory pressure.

Cardiopulmonary bypass (CPB) causes lung injury that occasionally progresses to the adult respiratory distress syndrome (ARDS). We measured the effect of 10 cmH2O of positive end-expiratory pressure (PEEP) on small solute and protein flux in dogs 1 wk before and 2 h after the completion of CPB. As an index of alveolar epithelial permeability, the clearance from lung to blood of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) was measured. To assess microvascular endothelial integrity, the rate of accumulation in the lung interstitium of intravascular 113mIn-transferrin was measured. The clearance half time (t 1/2) for 99mTc-DTPA in the study dogs declined from 18.8 +/- 1.9 min (mean +/- SE) at base line to 9.4 +/- 2.0 min during PEEP (P less than 0.05). Two hours after CPB, the t 1/2 was 8.1 +/- 1.6 min at base line and unchanged during PEEP. The 113mIn-transferrin rate of accumulation was unchanged by PEEP before CPB. After CPB, the index was 3.25 +/- 0.95 slope/min X 10(-3) (P less than 0.05). Of the five dogs with a significant slope, four showed a decrease in microvascular flux during PEEP, although for the group the mean change in slope was not significant (P = 0.10). We conclude that the application of PEEP does not increase 99mTc-DTPA clearance in lungs already injured by CPB, and may actually decrease the apparent microvascular protein flux in some cases.

Lobar collapse due to endobronchial metastatic prostatic carcinoma: re-expansion with antiandrogen treatment.

A patient is described who presented with left upper lobe collapse due to endobronchial metastatic prostate carcinoma. Treatment with the oral antiandrogen cyproterone acetate resulted in resolution of the occluding endobronchial carcinoma and lobar re-expansion.

Influenza A infection with rhabdomyolysis and acute renal failure--a potentially fatal complication.

This paper describes a case of influenza A infection complicated by rhabdomyolysis and acute renal failure. This very rare complication is particularly important as symptoms may be non-specific and therefore ascribed to the underlying influenzal illness.

Infused salbutamol accentuates acid-induced lung injury in the rat.

The effect in the rat of salbutamol infusion (1 microgram min-1 kg-1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 +/- 2.6 min) compared with non-acid-treated rats (98.1 +/- 7.2) (P less than 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 +/- 1.9) than the acid and control infusion group (P less than 0.05). Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 +/- 0.3) compared with the non-acid-treated controls (5.4 +/- 0.2) (P less than 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 +/- 0.6) (P less than 0.001 vs acid and control infusion). Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include beta 2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant beta 1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.

Tumour microembolism presenting as "primary pulmonary hypertension".

Pulmonary tumour microembolism is a rare cause of pulmonary hypertension. A case of rapidly progressive pulmonary hypertension in a patient with a past history of breast carcinoma is presented. Despite active consideration and investigation for malignancy as a cause, correct diagnosis was only made at necropsy.

Lymphoedema/hypercalcaemia syndrome mediated by parathyroid-hormone-related protein.

A 24-year-old woman presented with a cryptogenic, hypercalcaemic syndrome with metastatic pulmonary calcification and leg and massive breast enlargement and bilateral chylous pleural effusions compatible with a generalised lymphatic abnormality. The patient's serum parathyroid hormone-related protein concentration was very high at a time when she was significantly hypercalcaemic, implying that the hypercalcaemia was mediated by this protein.

Refractory hypoxaemia after pneumonectomy: diagnosis by transoesophageal echocardiography.

A patient with normal oxygenation before operation became very breathless and hypoxaemic after a right pneumonectomy. Transoesophageal echocardiography showed right to left interatrial shunting due to a patent foramen ovale. Transoesophageal echocardiography should be included in the assessment of patients who became inappropriately dyspnoeic after pneumonectomy.

Persistent, progressive hypophosphataemia after voluntary hyperventilation.

Hyperventilation (HV) and respiratory alkalosis are associated with hypophosphataemia, although the extent and duration of HV required to produce changes in serum phosphate levels are not known. We sought to characterize the effects of HV, with or without dextrose loading, on serum phosphate levels and other biochemical parameters. HV was monitored by controlling the end-tidal partial pressure of carbon dioxide (PETCO(2)). The effect of dextrose was studied because infusion of a glucose load is known to promote a fall in serum phosphate via stimulation of glycolysis. Eight healthy volunteers were enrolled in four study protocols: (1) HV for 20 min to a PETCO(2) of 25-30 mmHg (mild); (2) HV for 20 min to a PETCO(2) of 15-20 mmHg (severe); (3) mild HV with intravenous dextrose loading, and (4) dextrose loading alone. Periodic measurements of serum phosphate, venous pH, serum 2,3-diphosphoglycerate (2,3-DPG) and other parameters were made. Serum phosphate fell during HV and continued to decline after cessation of HV. Dextrose loading alone caused a fall in serum phosphate that continued for at least 30 min after cessation of the infusion (P<0.0002). HV combined with dextrose resulted in a greater decline in serum phosphate than either variable alone (P=0.003). The maximal decline in serum phosphate occurred in severe HV, with a mean decrease of 0.38 mmol/l at 20 min after cessation of HV (P<0.0001). Serum phosphate was still significantly lowered compared with baseline at 90 min after cessation of HV (P=0.001). Other significant changes seen with HV included a decrease in serum glucose (P<0.01), a decrease in serum potassium (P<0.05) and an increase in venous pH (P<0.007). Serum 2, 3-DPG levels did not change significantly in any study protocol. Thus relatively mild acute HV produces significant changes in serum phosphate. In both mild and severe HV this effect is progressive after cessation of HV. This phenomenon has not been shown before, and may have significant clinical implications.