A trial of nebulised heparin to limit lung injury following cardiac surgery.

Cardiac surgery with cardiopulmonary bypass triggers an acute inflammatory response in the lungs. This response gives rise to fibrin deposition in the microvasculature and alveoli of the lungs. Fibrin deposition in the microvasculature increases alveolar dead space, while fibrin deposition in alveoli causes shunting. We investigated whether prophylactic nebulised heparin could limit this form of lung injury. We undertook a single-centre double-blind randomised trial. Forty patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomised to prophylactic nebulised heparin (50,000 U) or placebo. The primary endpoint was the change in arterial oxygen levels over the operative period. Secondary endpoints included end-tidal CO2, the alveolar dead space fraction and bleeding complications. We found nebulised heparin did not improve arterial oxygen levels. Nebulised heparin was, however, associated with a lower alveolar dead space fraction (P <0.05) and lower tidal volumes at the end of surgery (P <0.01). Nebulised heparin was not associated with bleeding complications. In conclusion, prophylactic nebulised heparin did not improve oxygenation, but was associated with evidence of better alveolar perfusion and CO2elimination at the end of surgery.

Medical emergencies in the imaging department of a university hospital: event and imaging characteristics.

We aimed to describe the characteristics of medical emergencies that occurred in the medical imaging department (MID) of a university hospital in Melbourne, Australia. A database of 'Respond Medical Emergency Team (MET)' and 'Respond Blue' calls was retrospectively examined for the period June 2003 to November 2010 in relation to events that occurred in the MID. The hospital medical imaging database was also examined in relation to these events and, where necessary, patients' notes were reviewed. Ethics approval was granted by the hospital ethics review board. There were 124 medical emergency calls in the MID during the study period, 28% Respond Blue and 72% Respond MET. Of these 124 calls, 26% occurred outside of usual work hours and 12% involved cardiac arrest. The most common reasons for the emergency calls were seizures (14%) and altered conscious state (13%). Contrast anaphylaxis precipitated the emergency in 4% of cases. In 83% of cases the emergency calls were for patients attending the MID for diagnostic imaging, the remainder being for a procedure. Of the scheduled imaging techniques, 45% were for computed tomography. The scheduled imaging was abandoned due to the emergency in 12% of cases. When performed, imaging informed patient management in 34% of cases in diagnostic imaging and in all cases in the context of image-guided procedures. Medical emergency calls in the MID often occurred outside usual work hours and were attributed to a range of medical problems. The emergencies occurred in relation to all imaging techniques and imaging informed patient management in many cases.

Factors associated with increased risk of readmission to intensive care in Australia.

PURPOSE: To determine the epidemiology, in-hospital mortality, trends, patient characteristics and predictors of intensive care unit (ICU) readmission in Australia. METHODS: A retrospective longitudinal study of data for 38 Australian ICUs extracted from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS-ADP) for the years 2000-2007. Demographic, diagnostic, physiological and outcome data were analysed. A multivariate model was constructed to identify risk factors for ICU readmission. Outcomes examined included observed and risk-adjusted in-hospital mortality. RESULTS: A total of 247,103 patients were discharged alive from their first ICU admission; 13,598 (5.5%) were readmitted at least once. Variables associated with an odds ratio greater than 1.05 for readmission (p < 0.001) were an initial ICU admission source other than elective surgery, any chronic health variable on severity scoring, tertiary hospital ICU and discharge between 6 p.m. and 6 a.m. Five initial diagnoses were associated with an odds ratio (OR) greater than 2 for readmission (p < 0.001). In-hospital mortality in readmitted patients was 20.7% compared with 4.4% in those not readmitted. Readmission rates have not changed over the study period. After adjustment for illness severity and readmission propensity, ICU readmission remained significantly associated with in-hospital mortality (OR 5.4, 95%, confidence interval (CI) 5.1-5.7). CONCLUSIONS: Many risk factors for increased ICU readmission were identified in this study including ICU discharge between 6 p.m. and 6 a.m. This was the only modifiable variable studied. Prospective studies are required to identify other factors and to determine whether interventions may reduce ICU readmission and its high associated in-hospital mortality.

Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes.

AIMS: To assess the clinical features, pathology, mortality (systemic outcome) and ocular complications (visual outcome) of a cohort of patients treated for intraocular lymphoma. METHODS: Retrospective case analysis of medical records and review of pathology of a consecutive series of patients presenting with intraocular lymphoma in Melbourne over 11 years between 1990 and 2000. Categorical factors influencing survival were examined by the Kaplan-Meier estimator and groups compared with the log rank test. RESULTS: A total of 14 patients were included. The median age of onset of symptoms was 62.5 years. Most were male (64%) and had bilateral eye involvement (64%). The commonest presentation was vitritis in 12 patients, with a median delay of 4 months before diagnosis. In all, 10 patients had B-cell lymphoma, three patients T-cell lymphoma and one null-cell. Four patients had prior systemic lymphoma. Eight patients had primary central nervous system non-Hodgkin's lymphoma (PCNSL). Treatment included combined radiation to the eye and chemotherapy in 10 patients. Complications of radiotherapy included cataract in five (50%), dry eyes in four (40%), punctate keratopathy in two (20%), radiation retinopathy in two (20%), and optic atrophy in one (10%). A total of 11 patients died of lymphoma (79%). One has residual ocular disease, while two have survived for more than 5 years from initial presentation. Although currently disease free, one of these has a poor visual outcome with acuity less than 6/60 secondary to ocular complications of treatment. CONCLUSIONS: Our study had 29% with prior systemic lymphoma, 57% associated with PCNSL and 14% with intraocular disease only. Overall survival is low (21%) and relapses common in those surviving beyond 12 months. Visual outcome in survivors is very poor due, in large part, to significant complications from radiotherapy.

Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans.

We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB.

Early extubation after cardiac surgery: emotional status in the early postoperative period.

OBJECTIVE: To compare the emotional state during the first 3 days after coronary artery surgery of patients who had undergone early versus conventional extubation. DESIGN: A prospective, randomized, controlled trial. SETTING: University hospital, single center. PARTICIPANTS: Eligible patients (n = 100) presenting for elective coronary artery surgery, randomized to an early extubation group or a conventional extubation group. INTERVENTIONS: Emotional status was measured by the Hospital Anxiety and Depression Scale (HAD), the Self Assessment Manikin (SAM), and the Multiple Affect Adjective Check List-Revised (MAACL-R). Tests were administered preoperatively and on the 1st and 3rd days postoperatively. MEASUREMENTS AND MAIN RESULTS: Of patients in the conventional extubation group, 30% showed moderate-to-severe depressive symptoms (HAD score >10) on day 3 postoperatively compared with 8% of patients in the early extubation group (p = 0.02). There was a clinically insignificant increase in MAACL-R depression score on the 1st postoperative day within both groups but no other differences within or between groups in SAM or MAACL-R scores. CONCLUSION: Early extubation results in fewer patients displaying depressive symptoms on the 3rd postoperative day but appears to have little effect on other measurements of emotional status. Anesthetic management during coronary artery bypass graft surgery may play an important role in the overall well-being of the patient by decreasing the incidence of postoperative depression.

A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration.

OBJECTIVE: To compare the efficacy, safety, and cost of fixed-dose low-molecular-weight heparin (dalteparin) with adjusted-dose unfractionated heparin as anticoagulant for continuous hemofiltration. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: University-affiliated adult intensive care unit PATIENTS: All patients requiring continuous hemofiltration for acute renal failure or systemic inflammatory response syndrome (SIRS) were eligible. Fifty-seven patients were enrolled. Eleven were excluded, seven because of major protocol violations and four died before hemofiltration. INTERVENTIONS: Patients received continuous venovenous hemodialysis with filtration with prefilter replacement at 500 mL/hr and countercurrent dialysate at 1000 mL/hr. Filters were primed with normal saline containing anticoagulant. Dalteparin-treated patients received a commencement bolus of 20 units/kg and a maintenance infusion at 10 units/kg/hr. Heparin-treated patients received a commencement bolus of 2000-5000 units and a maintenance infusion at 10 units/kg/hr, titrated to achieve an activated partial thromboplastin time in the patient of 70-80 secs. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure--time to failure of the hemofilter--was compared using survival analysis. Twenty-two patients (13 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to heparin. Twenty-five patients (16 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to dalteparin. Mean (SE) activated partial thromboplastin time in the heparin group was 79 (4.3) secs. Mean (SE) anti-factor-Xa activity in the six patients given dalteparin who were assayed was 0.49 (0.07). Mean (SE) prehemofiltration platelet count was 225 (35.5) x 10(9) for heparin and 178 (18.1) x 10(9) for dalteparin (p = .24, unpaired Student's t-test). Mean (SE) prehemofiltration hemoglobin was 11.4 (0.61) g/dL for heparin and 10.6 (0.38) g/dL for dalteparin (p = .31, unpaired Student's t-test). PRIMARY OUTCOME: There was no significant difference in the time to failure between the two groups (p = .75, log rank test). For dalteparin, Kaplan-Meier (K-M) mean (SE) time to failure of the hemofilter was 46.8 (5.03) hrs. For heparin, K-M mean (SE) time to failure was 51.7 (7.51) hrs. The 95% CI for difference in mean time to failure was -13 to 23 hrs. The power of this study to detect a 50% change in filter life was >90%. SECONDARY OUTCOMES: Mean (SE) reduction in platelet count during hemofiltration was 63 (25.8) x 10(9) for heparin and 41.8 (26.6) x 10(9) for dalteparin (p = .57, unpaired Student's t-test). Eight patients given dalteparin and four patients given heparin had screening for heparin-induced thrombocytopenia; three of the dalteparin patients and one of the heparin patients were positive (p = 1.0, Fisher's exact test). There were three episodes of trivial bleeding and two episodes of significant bleeding for dalteparin, and there were three episodes of trivial bleeding and four episodes of significant bleeding for heparin (p = .53, chi-square test). The mean (SE) decrease in hemoglobin concentration during hemofiltration was 0.51 (0.54) g/dL for heparin and 0.28 (0.49) g/dL for dalteparin (p = .75, unpaired Student's t-test). The mean (SE) packed-cell transfusion volume during hemofiltration was 309 (128) mL for heparin and 290 (87) mL for dalteparin (p = .90, unpaired Student's t-test). Daily costs, including coagulation assays, of hemofiltration were approximately 10% higher using dalteparin than with heparin. CONCLUSIONS: Fixed-dose dalteparin provided identical filter life, comparable safety, but increased total daily cost compared with adjusted-dose heparin. Unfractionated heparin remains our anticoagulant of choice for continuous hemofiltration in intensive care.

Early extubation following coronary artery bypass surgery: a prospective randomized controlled trial. The Fast Track Cardiac Care Team.

STUDY OBJECTIVES: To determine the safety of early extubation (EE) after coronary artery surgery. DESIGN: Prospective randomized controlled trial. SETTING: The cardiac surgery operating room and ICU of a university-affiliated teaching hospital. PATIENTS: One hundred eligible patients presenting for elective coronary artery surgery. INTERVENTIONS: Patients randomized to the EE group were administered a reduced dose of fentanyl (15 microg/kg) and an anesthetic compatible with EE, while patients randomized to the conventional extubation (CE) group were given fentanyl (50 microg/kg). MEASUREMENTS AND RESULTS: The time to extubation in the EE group (median, 240 min; range, 30 to 930 min) was significantly less than the CE group (median, 420 min; range, 125 to 1,140 min) (p<0.01). Twenty patients were withdrawn from the study according to protocol guidelines. There were no cases of reintubation or complications attributable to EE. CONCLUSIONS: By using an appropriate anesthetic technique and postoperative management, EE can be achieved following coronary artery bypass surgery without major complications.

Current status of coronary artery bypass grafting in patients 70 years of age and older.

One hundred and seventy patients 70 years of age and older underwent isolated coronary artery bypass grafting (CABG) from January 1990 to December 1991 at St. Vincent's Hospital, Melbourne, Australia. The clinical records of these patients were analysed to investigate whether elderly patients could undergo safe coronary artery surgery and to determine the factors affecting the outcome. The 30 day or in-hospital mortality was 2.9% (5/170), with 80% (4/5) of the deaths due to cardiac causes. Major postoperative complications occurred in 22.3% (38/170) patients. The median postoperative hospital stay for the patients was 8 days (range 3-103 days). Univariate analysis identified hypertension and female gender as pre-operative risk factors and intraaortic balloon pump, prolonged ventilation, infarct, tamponade, need for inotropes, renal failure and a high APACHE II scores in the intensive care unit as postoperative significant risk factors for operative mortality. There was a trend towards increased mortality with emergency operations; the operative mortality was 2.1% (2/97) for elective operations, 3.1% (2/64) in urgent cases and 11.1% (1/9) for emergencies. Multivariate logistic regression analysis identified prolonged mechanical ventilation, perioperative infarct and APACHE II score as significant independent predictors of mortality. The low operative mortality indicates that elderly patients can undergo safe revascularization. A high incidence of complications necessitates careful monitoring but age per se should not be considered a contraindication to isolated CABG.

Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/l, 95% confidence interval 117-324) and albuminuria (n = 19, 281 U/l, 165-479) were higher than in non-diabetic control subjects (n = 140, 107 U/l, 85-134, p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/l, 76-169, p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40, 193 U/l, 126-298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/l, 143-306 vs n = 54, 116 U/l, 78-173, p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.

Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD).

The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study.

Optimisation of respiratory function.

OBJECTIVE: To apply pathophysiological principles in the management of patients with acute and chronic respiratory impairment. CONCLUSIONS: Knowledge of the pathophysiology of respiratory disorders is a key element in treatment of patients with impending or established respiratory failure. Therapies to improve and support abnormal gas exchange will minimise the complications of hypoxia and interventions to optimise ventilation and work of breathing may obviate the need for mechanical ventilation.

Reversible reproductive dysfunction in men with obstructive sleep apnoea.

A central, reversible decrease in male sexual function appears related to some aspect of obstructive sleep apnoea (OSA). Lower serum testosterone (T) levels were documented in 15 men with OSA versus nine snorers (no OSA), (9.18 +/- 0.92 vs 11.55 +/- 0.90 nmol/l, mean +/- SEM), P less than 0.05 in a consecutive case series of 24 men referred for diagnostic overnight sleep studies. Gonadotrophins did not differ between the two groups. Although the men with OSA did not differ in body mass index (BMI) or weight from the snorers, they were older (51 +/- 3.9 vs 44 +/- 3.1 years), P less than 0.02. Serum T did not correlate with age, but was correlated with minimum nocturnal arterial oxygen saturation (Min SaO2) (r = 0.589), P less than 0.02. A prospective controlled trial of uvulopalatopharyngoplasty therapy (UPP) for OSA in 12 subsequent subjects showed reproductive improvement which was parallel with improved apnoea at 3 months postsurgery. T increased (13.31 +/- 1.07 to 16.59 +/- 0.72 nmol/l), P less than 0.02, without significant changes in BMI, serum PRL, LH or FSH. All seven of the men who reported decreased sexual interest prior to surgery felt their libido and sexual functioning had returned to normal 3 months following UPP. Some aspect of OSA in men appears to produce a reversible hypothalamic-pituitary reproductive dysfunction.

Facial morphology and obstructive sleep apnea.

In a sample of 25 adult male subjects with moderate to severe obstructive sleep apnea, the interaction among craniofacial, airway, tongue, and hyoid variables was quantified by means of a canonical correlation analysis. One lateral cephalometric radiograph with the teeth in occlusion was obtained for each subject together with overnight polysomnographic measurements before the initiation of therapy. A principal component analysis reduced the data base and one significant canonical correlation (r1 = 0.994) was identified for the 22 variables. Sleep apnea subjects showed a posteriorly positioned maxilla and mandible, a steep occlusal plane, overerupted maxillary and mandibular teeth, proclined incisors, a steep mandibular plane, a large gonial angle, high upper and lower facial heights, and an anterior open bite in association with a long tongue and a posteriorly placed pharyngeal wall. A multivariate statistical analysis extracted clinically significant associations among craniofacial, tongue, and airway variables. Subjects with sleep apnea demonstrated several alterations in craniofacial form that may reduce the upper airway dimensions and subsequently impair upper airway stability.

Patient comfort and plasma lignocaine concentrations during fibreoptic bronchoscopy.

In a preliminary prospective study, eleven outpatients undergoing fibreoptic bronchoscopy using a titrated dose of topical lignocaine anaesthesia were studied. Patient comfort, lignocaine dosage and resultant plasma concentrations were measured at four stages during the procedure. Large total doses, mean 512 (SD 55) mg lignocaine, were frequent and systemic absorption was unpredictable with two patients having plasma concentrations in the toxic range (greater than 5 micrograms/ml). Peak plasma concentrations, mean 2.3 (SD 1.4) micrograms/ml, occurred 30 to 40 minutes after commencement of topical application and coincided with completion of the procedure. No correlation was found between the individual dose of lignocaine administered and either the resultant plasma concentration or patient comfort scores. In an effort to minimise potential lignocaine toxicity, a fixed total dose technique (lignocaine 370 mg) was studied in a further twenty-one patients. No change in patient comfort scores and no toxic plasma concentrations were observed. Mean completion plasma concentration was 2.0 (SD 1.0) micrograms/ml. No clinical toxicity was observed in either group. Fibreoptic bronchoscopy in both groups using topical lignocaine anaesthesia without premedication or intravenous supplementation was well tolerated.

The potential bronchodilator action of verapamil.

Although calcium antagonists such as verapamil are used primarily in cardiovascular disease, they appear to relax smooth muscle generally. Therefore, the possibility that verapamil might have bronchodilator properties was explored using the guinea-pig tracheal ring technique. Verapamil was found to produce considerable tracheal smooth muscle relaxation from a threshold concentration of 2 X 10(-7) M and with maximum effect at 10(-3) M. The responses to the contractile agonists histamine and prostaglandin F2 alpha and especially methacholine and serotonin were substantially reduced by prior administration of verapamil. Verapamil 2 X 10(-4) M was equally effective as isoprenaline 10(-8) M in producing 50% maximum direct relaxation but was more effective than isoprenaline as an antagonist of the contractile agonists, methacholine, histamine and serotonin, but not prostaglandin F2 alpha. Verapamil abolished the contractile responses to barium chloride. It is concluded that, although verapamil was not very potent as a direct bronchodilator, it could potentially be of prophylactic benefit in asthma because of its efficacy as an antagonist of common contractile agonists.