Year in review 2005: Critical Care – Respirology: mechanical ventilation, infection, monitoring, and education

We summarize all original research in the field of respiratory intensive care medicine published in 2005 in Critical Care. Twenty-seven articles were grouped into the following categories and subcategories to facilitate rapid overview: mechanical ventilation (physiology, spontaneous breathing during mechanical ventilation, high frequency oscillatory ventilation, side effects of mechanical ventilation, sedation, and prone positioning); infection (pneumonia and sepsis); monitoring (ventilatory monitoring, pulmonary artery catheter and pulse oxymeter); and education (training and health outcome)

Human SP-A and a pharmacy-grade porcine lung surfactant extract can be reconstituted into tubular myelin--a comparative structural study of alveolar surfactants using cryo-transmission electron microscopy.

Cryo-transmission electron microscopy (cryo-TEM) is a rather artefact-free method, well suited to study the alveolar surfactant system. A pharmacy grade porcine lung surfactant extract (HL-10) was mixed with human SP-A and Ringer's solution (for calcium ions), and it was shown by cryo-TEM that the tubular myelin (TM) type of structure was reconstituted. These aggregates were associated to liposomal aggregates, and resulted in macroscopic phase-separation. This phase showed a weak birefringence in the polarising microscope, which is characteristic for a liquid-crystalline type of structure. TM from rabbit lung lavage was also examined, and showed the same periodic arrangement of bilayers as alveolar surface layer from freshly cut rabbit lungs deposited directly on the cryo-TEM grids. The distance between the bilayers of TM was 40-50 nm, and an electron dense material, assumed to be SP-A, was sometimes seen to occur periodically along the bilayers, oriented perpendicularly to the tubuli. The results are consistent with the surface-phase model of the alveolar lining

Access to anti-cancer drugs in India: Is there a need to revise reimbursement policies?

The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India.Methods: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines. Direct medical costs and shortage of budget in reimbursed amounts were calculated for each listed chemotherapy regimen.Results: Medical oncology practice following the schemes’ formularies is inferior to recommendations by the NCCN guidelines. Innovative treatment (targeted therapies) like trastuzumab, pertuzumab (breast), bevacizumab, cetuximab, panitumumab (colorectal), erlotinib, gefitinib, crizotinib, and nivolumab (lung) are either not reimbursed (VAS, CMCHS) or partially reimbursed (RAS). Average shortage of budget was found to be 43% (breast), 55% (colorectal), 74% (lung), 7% (head & neck), and 51% (gastric cancer).Conclusions: Policy makers should consider addition of newer treatments, exclusion of sub-optimal treatments, increments in per patient budget and optimization of supportive care, which may contribute to improvements in survival and quality of life for Indian cancer patients

How to achieve robustness against scaling in a real-time digital watermarking system for broadcast monitoring

In the European Esprit project VIVA (Visual Identity Verification Auditor) a real-time digital watermarking system for broadcast monitoring has been investigated and implemented. On top of the usual requirements for watermarks, the VIVA watermarking system has to satisfy an additional number of constraints. One of the most important constraints in a broadcast environment is the robustness of the watermark against scaling. This paper describes how robustness against scaling is achieved in the VIVA project. Furthermore, a real-time implementation of the algorithms is discussed. Experimental results prove the effectiveness of the algorithms

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046

1. In view of the potential therapeutic application of specific dopamine receptor agonists in the treatment of hypertension and left ventricular dysfunction, we investigated the cardiovascular actions of the novel mixed D1/D2 dopamine receptor agonist Z1046 in awake pigs at rest and during treadmill exercise. 2. Thirteen swine were chronically instrumented under sterile conditions for measurement of systemic, pulmonary, and coronary haemodynamics. Regional blood flows were determined with the radioactive microsphere technique. 3. Z1046 (1, 10, 100 μg kg-1, i.v.) produced dose-dependent reductions in central aortic blood pressure (up to 27 ± 3%, P ≤ 0.05) in awake resting pigs which was accompanied by only minimal reflex activation of the sympathetic nervous system. The hypotensive response was principally the result of peripheral vasodilatation (system vascular resistance decreased up to 35 ± 4%, P ≤ 0.05), which was located in the cerebral, coronary, renal, mesenteric, adrenal, splenic and skeletal muscular vascular beds (vascular resistance decreased up to 30-40% after the highest dose in these beds). Only in the cerebral and mesenteric bed was the vasodilatation sufficiently large to overcome the decrease in blood pressure and result in an increased blood flow; the vasodilatation in the coronary bed was most likely due to autoregulation as neither coronary blood flow nor myocardial oxygen demand were changed significantly by Z1046. The systemic vasodilatation that was caused by the highest i.v. dose (100 μg kg-1) was accompanied by transient and minor increases in heart rate (15 ± 5%, P ≤ 0.05) and cardiac output (15 ± 5%, P ≤ 0.05) whereas after 10 μg kg-1, i.v., a slight decrease in cardiac output also contributed to the hypotension. Z1046 had no effect on pulmonary vascular resistance. 4. The systemic vasodilator responses to Z1046 (100 μg kg-1, i.v.) were sustained during treadmill exercise (2-4 km h-1 which produced heart rates of up to 233 ± 10 beats min-1), but with increasing treadmill speed attenuation of the exercise-induced increase in heart rate (-11 ± 3%, P ≤ 0.05) and hence cardiac output (-10 ± 3%, P ≤ 0.05) (as stroke volume was not altered by Z1046) contributed significantly to a lower aortic blood pressure (-20 ± 3%, P ≤ 0.05). Z1046 had no effect on pulmonary vascular resistance during exercise. 5. Oral administration of Z1046 (0.5, 1.5 mg kg-1) produced a fall in central aortic blood pressure (up to 15 ± 3%, P ≤ 0.05), which developed gradually during the first 90 min and lasted up to 4 h after administration, again with negligible changes in heart rate and LVdP/dt(max). 6. Neither non-selective α- and β-adrenoceptor blockade, nor selective α2-adrenoceptor blockade altered the vasodilator actions of Z1046, but non-selective α- and β-adrenoceptor blockade abolished the cardiac responses to dopamine receptor stimulation, suggesting that its cardiac actions were principally caused by D2-receptor-mediated inhibition of catecholamine release, whereas the vasodilator response was probably the result of vascular D1-receptor stimulation. 7. In conclusion, the novel dopamine receptor agonist Z1046 is an effective blood pressure lowering agent that elicits minimal reflex activation of the sympathetic nervous system in awake resting pigs. Systemic vasodilatation was not affected by combined α- and β-adrenoceptor blockade, which is consistent with a predominantly D1 receptor-dependent vasodilator mechanism. The hypotensive effect is maintained during treadmill exercise during which systemic vasodilatation and a lower cardiac output both contribute to the blood pressure lowering actions of Z1046. The cardiovascular profile of this orally active compound warrants further investigation of this class of drugs in experimental and clinical hypertension.</p

How to achieve robustness against scaling in a real-time digital watermarking system for broadcast monitoring

In the European Esprit project VIVA (Visual Identity Verification Auditor) a real-time digital watermarking system for broadcast monitoring has been investigated and implemented. On top of the usual requirements for watermarks, the VIVA watermarking system has to satisfy an additional number of constraints. One of the most important constraints in a broadcast environment is the robustness of the watermark against scaling. This paper describes how robustness against scaling is achieved in the VIVA project. Furthermore, a real-time implementation of the algorithms is discussed. Experimental results prove the effectiveness of the algorithms

How to achieve robustness against scaling in a real-time digital watermarking system for broadcast monitoring

In the European Esprit project VIVA (Visual Identity Verification Auditor) a real-time digital watermarking system for broadcast monitoring has been investigated and implemented. On top of the usual requirements for watermarks, the VIVA watermarking system has to satisfy an additional number of constraints. One of the most important constraints in a broadcast environment is the robustness of the watermark against scaling. This paper describes how robustness against scaling is achieved in the VIVA project. Furthermore, a real-time implementation of the algorithms is discussed. Experimental results prove the effectiveness of the algorithms

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046

1. In view of the potential therapeutic application of specific dopamine receptor agonists in the treatment of hypertension and left ventricular dysfunction, we investigated the cardiovascular actions of the novel mixed D1/D2 dopamine receptor agonist Z1046 in awake pigs at rest and during treadmill exercise. 2. Thirteen swine were chronically instrumented under sterile conditions for measurement of systemic, pulmonary, and coronary haemodynamics. Regional blood flows were determined with the radioactive microsphere technique. 3. Z1046 (1, 10, 100 μg kg-1, i.v.) produced dose-dependent reductions in central aortic blood pressure (up to 27 ± 3%, P ≤ 0.05) in awake resting pigs which was accompanied by only minimal reflex activation of the sympathetic nervous system. The hypotensive response was principally the result of peripheral vasodilatation (system vascular resistance decreased up to 35 ± 4%, P ≤ 0.05), which was located in the cerebral, coronary, renal, mesenteric, adrenal, splenic and skeletal muscular vascular beds (vascular resistance decreased up to 30-40% after the highest dose in these beds). Only in the cerebral and mesenteric bed was the vasodilatation sufficiently large to overcome the decrease in blood pressure and result in an increased blood flow; the vasodilatation in the coronary bed was most likely due to autoregulation as neither coronary blood flow nor myocardial oxygen demand were changed significantly by Z1046. The systemic vasodilatation that was caused by the highest i.v. dose (100 μg kg-1) was accompanied by transient and minor increases in heart rate (15 ± 5%, P ≤ 0.05) and cardiac output (15 ± 5%, P ≤ 0.05) whereas after 10 μg kg-1, i.v., a slight decrease in cardiac output also contributed to the hypotension. Z1046 had no effect on pulmonary vascular resistance. 4. The systemic vasodilator responses to Z1046 (100 μg kg-1, i.v.) were sustained during treadmill exercise (2-4 km h-1 which produced heart rates of up to 233 ± 10 beats min-1), but with increasing treadmill speed attenuation of the exercise-induced increase in heart rate (-11 ± 3%, P ≤ 0.05) and hence cardiac output (-10 ± 3%, P ≤ 0.05) (as stroke volume was not altered by Z1046) contributed significantly to a lower aortic blood pressure (-20 ± 3%, P ≤ 0.05). Z1046 had no effect on pulmonary vascular resistance during exercise. 5. Oral administration of Z1046 (0.5, 1.5 mg kg-1) produced a fall in central aortic blood pressure (up to 15 ± 3%, P ≤ 0.05), which developed gradually during the first 90 min and lasted up to 4 h after administration, again with negligible changes in heart rate and LVdP/dt(max). 6. Neither non-selective α- and β-adrenoceptor blockade, nor selective α2-adrenoceptor blockade altered the vasodilator actions of Z1046, but non-selective α- and β-adrenoceptor blockade abolished the cardiac responses to dopamine receptor stimulation, suggesting that its cardiac actions were principally caused by D2-receptor-mediated inhibition of catecholamine release, whereas the vasodilator response was probably the result of vascular D1-receptor stimulation. 7. In conclusion, the novel dopamine receptor agonist Z1046 is an effective blood pressure lowering agent that elicits minimal reflex activation of the sympathetic nervous system in awake resting pigs. Systemic vasodilatation was not affected by combined α- and β-adrenoceptor blockade, which is consistent with a predominantly D1 receptor-dependent vasodilator mechanism. The hypotensive effect is maintained during treadmill exercise during which systemic vasodilatation and a lower cardiac output both contribute to the blood pressure lowering actions of Z1046. The cardiovascular profile of this orally active compound warrants further investigation of this class of drugs in experimental and clinical hypertension.</p

Multicenter Evaluation of the Course of Coagulopathy in Patients with Isolated Traumatic Brain Injury:Relation to CT Characteristics and Outcome

This prospective multicenter study investigated the association of the course of coagulation abnormalities with initial computed tomography (CT) characteristics and outcome in patients with isolated traumatic brain injury (TBI). Patient demographics, coagulation parameters, CT characteristics, and outcome data of moderate and severe TBI patients without major extracranial injuries were prospectively collected. Coagulopathy was defined as absent, early but temporary, delayed, or early and sustained. Delayed/sustained coagulopathy was associated with a higher incidence of disturbed pupillary responses (40% versus 27%; p<0.001) and higher Traumatic Coma Data Bank (TCDB) CT classification (5 (2-5) versus 2 (1-5); p=0.003) than in patients without or with early, but short-lasting coagulopathy. The initial CT of patients with delayed/sustained coagulopathy more frequently showed intracranial hemorrhage and signs of raised intracranial pressure (ICP) compared to patients with early coagulopathy only. This was paralleled by higher in-hospital mortality rates (51% versus 33%; p<0.05), and poorer 6-month functional outcome in patients with delayed/sustained coagulopathy. The relative risk for in-hospital mortality was particularly related to disturbed pupillary responses (OR 8.19; 95% CI 3.15,21.32; p<0.001), early, short-lasting coagulopathy (OR 6.70; 95% CI 1.74,25.78; p=0.006), or delayed/sustained coagulopathy (OR 5.25; 95% CI 2.06,13.40; p=0.001). Delayed/sustained coagulopathy is more frequently associated with CT abnormalities and unfavorable outcome at 6 months after TBI than early, short-lasting coagulopathy. Our finding that not only the mere presence but also the time course of coagulopathy holds predictive value for patient outcome underlines the importance of systematic hemostatic monitoring over time in TBI