Respiratory comfort and breathing pattern during volume proportional assist ventilation and pressure support ventilation: a study on volunteers with artificially reduced compliance

OBJECTIVE: To assess respiratory comfort and associated breathing pattern during volume assist (VA) as a component of proportional assist ventilation and during pressure support ventilation (PSV). DESIGN: Prospective, double-blind, interventional study. SETTING: Laboratory. SUBJECTS: A total of 15 healthy volunteers (11 females, 4 males) aged 21-31 yrs. INTERVENTIONS: Decreased respiratory system compliance was simulated by banding of the thorax and abdomen. Volunteers breathed via a mouthpiece with VA and PSV each applied at two levels (VA, 8 cm H2O/L and 12 cm H2O/L; PSV, 10 cm H2O and 15 cm H2O) using a positive end-expiratory pressure of 5 cm H2O throughout. The study was subdivided into two parts. In Part 1, volunteers breathed three times with each of the four settings for 2 mins in random order. In Part 2, the first breath effects of multiple, randomly applied mode, and level shifts were studied. MEASUREMENTS AND MAIN RESULTS: In Part 1, the volunteers were asked to estimate respiratory comfort in comparison with normal breathing using a visual analog scale. In Part 2, they were asked to estimate the change of respiratory comfort as increased, decreased, or unchanged immediately after a mode shift. Concomitantly, the respiratory pattern (change) was characterized with continuously measured tidal volume, respiratory rate, pressure, and gas flow. Respiratory comfort during VA was higher than during PSV. The higher support level was less important during VA but had a major negative influence on comfort during PSV. Both modes differed with respect to the associated breathing pattern. Variability of breathing was higher during VA than during PSV (Part 1). Changes in respiratory variables were associated with changes in respiratory comfort (Part 2). CONCLUSIONS: For volunteers breathing with artificially reduced respiratory system compliance, respiratory comfort is higher with VA than with PSV. This is probably caused by a better adaptation of the ventilatory support to the volunteer's need with VA.     

Effect of vasopressin and somatostatin on hemodynamics and blood gases in patients with liver cirrhosis

The effects of somatostatin and vasopressin on blood gases, pulmonary and systemic hemodynamics, and portal pressure assessed by the gradient between occluded and free hepatic vein pressures, were investigated in 18 patients with liver cirrhosis. In the first 10 patients, an iv bolus of 250 microgram somatostatin, followed by an infusion of 125 microgram somatostatin over 30 min, caused a sudden rise in pulmonary and systemic vascular pressures lasting 2 to 5 min and accompanied by bradycardia. There was a slight and transient increase in venous admixture (Qsp/Qt) and alveolar-arterial oxygen tension gradients (P(A-a)O2), and a transient reduction in O2 delivery (O2 del) (-11% of the baseline values) and portal pressures (-14%). In the next 8 patients, vasopressin, 0.4 U/min infused over 30 min, caused a more persistent pulmonary and systemic hypertension and bradycardia, a slight increase in P(A.a)O2 and Qsp/Qt, a reduction in O2 del (-27%) and a decrease in portal pressures (-32%). These effects were marked during the entire vasopressin infusion period. Both somatostatin and vasopressin had vasoconstrictive properties and exerted negative effects on hemodynamics and blood gases. Vasopressin appeared to be a more potent drug than somatostatin.     

Accuracy of automatic tube compensation in new-generation mechanical ventilators

OBJECTIVE: To compare performance of flow-adapted compensation of endotracheal tube resistance (automatic tube compensation, ATC) between the original ATC system and ATC systems incorporated in commercially available ventilators. DESIGN: Bench study. SETTING: University research laboratory. SUBJECTS: The original ATC system, Dr?ger Evita 2 prototype, Dr?ger Evita 4, Puritan-Bennett 840. INTERVENTIONS: The four ventilators under investigation were alternatively connected via different sized endotracheal tubes and an artificial trachea to an active lung model. Test conditions consisted of two ventilatory modes (ATC vs. continuous positive airway pressure), three different sized endotracheal tubes (inner diameter 7.0, 8.0, and 9.0 mm), two ventilatory rates (15/min and 30/min), and four levels of positive end-expiratory pressure (0, 5, 10, and 15 cm H2O). MEASUREMENTS AND MAIN RESULTS: Performance of tube compensation was assessed by the amount of tube-related (additional) work of breathing (WOBadd), which was calculated on the basis of pressure gradient across the endotracheal tube. Compared with continuous positive airway pressure, ATC reduced inspiratory WOBadd by 58%, 68%, 50%, and 97% when using the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. Depending on endotracheal tube diameter and ventilatory pattern, inspiratory WOBadd was 0.12-5.2 J/L with the original ATC system, 1.5-28.9 J/L with the Puritan-Bennett 840, 10.4-21.0 J/L with the Evita 2 prototype, and 10.1-36.1 J/L with the Evita 4 (difference between each ventilator at identical test situations, p <.025). Expiratory WOBadd was reduced by 5%, 26%, 1%, and 70% with the Evita 4, the Evita 2 prototype, the Puritan-Bennett 840, and the original ATC system, respectively. The expiratory WOBadd caused by an endotracheal tube of 7.0 mm inner diameter was 5.5-42.2 J/L at a low ventilatory rate and 19.6-82.3 J/L at a high ventilatory rate. It was lowest with the original ATC system and highest with the Evita 4 ventilator (p <.025). CONCLUSIONS: Flow-adapted tube compensation by the original ATC system significantly reduced tube-related inspiratory and expiratory work of breathing. The commercially available ATC modes investigated here may be adequate for inspiratory but probably not for expiratory tube compensation.     

Continuous calculation of intratracheal pressure in the presence of pediatric endotracheal tubes

OBJECTIVE: To measure the pressure-flow relationship of pediatric endotracheal tubes (ETTs) in trachea models, to mathematically describe this relationship, and to evaluate in trachea/lung models a method for calculation of pressure at the distal end of the ETT (Ptrach) by subtracting the flow-dependent pressure drop across the ETT from the airway pressure measured at the proximal end of the ETT. DESIGN: Trachea models and trachea/lung models. SETTING: Research laboratory in a university medical center. INTERVENTIONS: The pressure-flow relationship of pediatric ETTs (inner diameter, 2.5-6.5 mm) was determined using a physical model consisting of a tube connector, an anatomically curved ETT, and an artificial trachea. The model was ventilated with sinusoidal gas flow (12-60 cycles/min). The coefficients of an approximation equation considering ETT resistance and inertance were fitted separately to the measured pressure-flow curves for inspiration and expiration. Calculated Ptrach was compared with directly measured Ptrach in mechanically ventilated physical trachea/lung models. MEASUREMENTS AND MAIN RESULTS: The pressure-flow relationship was considerably nonlinear and showed hysteresis around the origin caused by the inertia of accelerated gas. ETT inertance ranged from 0.1 to 0.4 cm H2O/L x sec2 (inner diameter, 6-2.5 mm). The abrupt change in cross-sectional area at the tube connector caused an inspiration-to-expiration asymmetry. Calculated and measured Ptrach were within +/- 1 cm H2O. Correspondence between measured and calculated Ptrach is improved even further when the ETT inertance is taken into account. CONCLUSIONS: Ptrach can continuously be monitored in the presence of pediatric ETT by combining ETT coefficients and the flow and airway pressure continuously measured at the proximal end of the ETT.     

Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration

BACKGROUND: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. METHODS: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. RESULTS: Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12 h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 microg/L cutoff, longer than that of plasma (12-16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 microg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. CONCLUSIONS: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7-21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.     

Distinct histological features characterize primary angiosarcoma of bone

Verbeke S L J, Bertoni F, Bacchini P, Sciot R, Fletcher C D M, Kroon H M, Hogendoorn P C W & Bovée J V M G
(2011) Histopathology  58, 254–264
Distinct histological features characterize primary angiosarcoma of bone Aims: To define the histological criteria of primary angiosarcoma of bone. Methods and results: Forty‐two angiosarcomas of bone in 23 males and 15 females were studied. Histological criteria were related to patients’ outcome. Eleven patients had multifocal lesions. Lesions were located in the long and short tubular bones followed by the pelvis, spine and trunk. Tumour cells were positive for CD31 in 38 of 40, von Willebrand Factor in 21 of 35, CD34 in 15 of 38, smooth muscle actin in 22 of 36, D2–40 in 11 of 35 and keratinAE1AE3 in 27 of 39. Thirty‐nine tumours showed an epithelioid phenotype. One‐ and 5‐year survival rates were 55% and 33%, respectively. Survival analysis showed that a macronucleolus, three or more mitoses per 10 high‐power field (HPF) and fewer than five eosinophilic granulocytes per 10 HPF within a tumour was associated with an even worse survival compared to the overall group. Conclusions: Because keratin positivity is seen in the majority of cases, pathologists should avoid misinterpretation as metastatic carcinoma. A macronucleolus, three or more mitoses per 10 HPF and fewer than five eosinophilic granulocytes per 10 HPF can be used to further define angiosarcoma of bone.     

Impact of chemotherapy on health status and symptom burden of colon cancer survivors: a population-based study

Background

This population-based study assessed the impact of chemotherapy on general and disease-specific health status of resected colon cancer survivors up to 10 years post-diagnosis.

Patients and methods

Colon cancer survivors diagnosed between 1998 and 2007 were selected from the Eindhoven Cancer Registry. Survivors completed the SF-36 and the EORTC colorectal module (EORTC-QLQ-CR38). Comparisons to a normative population were conducted. Multiple linear regression analyses investigated the association between treatment and health status.

Results

Eight hundred and forty eight survivors were evaluated: 29% had chemotherapy (CT); 71% without chemotherapy (nCT). Survivors had similar SF-36 scores and scored better than the normative population on several domains. On the EORTC-QLQ-CR38, male nCT survivors had more sexual problems than CT survivors (p = 0.01). Among the sexually active respondents, the survivors reported sex to be less enjoyable than the normative population (p = 0.02). In multivariate analyses, CT predicted better physical function, and less male sexual dysfunction and weight loss problems than nCT.

Conclusions

Overall, CT survivors have general health status scores comparable to nCT survivors and the normative population up to 10 years since initial diagnosis. Sex-related problems among survivors suggest more attention on this often sensitive issue is required in clinical management.     

Subacute trismus in a kidney transplant recipient

This case report describes a male patient with trismus and generalized muscle weakness as the presenting symptom of disseminated malignancy. Trismus was caused by the presence of multiple small nests of undifferentiated tumor cells between muscle fibers of the masseter muscles as well as of other skeletal muscles. The diagnosis was suggested by increased uptake of 18-fluoro-deoxyglucose on positron emission tomography and subsequent ultrasound examination. The primary tumor was not found on autopsy. The patient was at increased risk for malignancy due to his renal transplantation 16 years before.     

Inflammation-induced changes in rostral ventromedial medulla mu and kappa opioid receptor mediated antinociception

Acute microinjection of mu-, delta-, or kappa-opioid receptor (MOPr, DOPr, KOPr) agonists into the rostral ventromedial medulla (RVM) produces antinociception. Thermal antinociception produced by MOPr and DOPr agonists is potentiated during inflammation [Hurley RW, Hammond DL. The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 2000;20:1249-59]. Whether this potentiation extends to other stimulus modalities or to KOPr agonists is unknown. To examine these issues, rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA). Antinociception produced by RVM infusion of the KOPr agonist, U69593, and the MOPr agonist, DAMGO, was tested 4h-2 weeks thereafter. Thermal paw withdrawal latencies (PWLs) were assessed using the Hargreaves method. Mechanical thresholds were determined with the Von Frey and Randall-Selitto method. PWLs of the inflamed paw were reduced 4h-2 weeks after CFA injection. Infusion of either U69593 or DAMGO increased PWLs in CFA treated rats. A bilateral enhancement of the response to both agonists was observed 2 weeks relative to 4h post-CFA injection. Mechanical thresholds of the inflamed paw were decreased for >2 weeks post-CFA injection. Infusion of either agonist elevated thresholds of the inflamed and non-inflamed paws of CFA-treated rats. The magnitude of these effects was greater 2 weeks post-CFA injection for DAMGO and increased progressively for U69593. These data demonstrate that RVM infusion of MOPr or KOPr agonists attenuates CFA-evoked thermal and tactile allodynia and that these effects increase during prolonged inflammation. The augmented response of the non-inflamed paw to agonists suggests that inflammation induces centrally-mediated neuroplastic changes which enhance MOPr- and KOPr-mediated antinociception.