Thomas Similowski

Contractile Properties of the Human Diaphragm during Chronic Hyperinflation

BACKGROUND In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.

Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study

ABSTRACT A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2[P = 0.026] and 414 versus 818 g2[P = 0.057], respectively). The 10-day treatment cost per patient was

Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients

454 ± 137 in the IIV group and was 23% lower in the CIV group (

Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation.

321 ± 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

Diaphragm Dysfunction on Admission to the Intensive Care Unit. Prevalence, Risk Factors, and Prognostic Impact—A Prospective Study

Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.

Is obstructive sleep apnea a problem in Parkinson's disease?

Objectives:To compare descriptors of the breath-to-breath respiratory variability during a 60-min spontaneous breathing trial in patients successfully and unsuccessfully separated from the ventilator and the endotracheal tube and to assess the usefulness of these predictors in discriminating these two categories of patients. Design:Prospective observational study. Setting:Four general intensive care units in university hospitals. Patients:A total of 51 consecutive patients mechanically ventilated for >24 hrs. Interventions:None. Measurements and Main Results:Tidal volume, respiratory period, inspiratory time, expiratory time, mean inspiratory flow (tidal volume/inspiratory time), and duty cycle (inspiratory time/respiratory period) were obtained from the flow signal. Breath-by-breath variability was expressed in terms of their coefficients of variation (CV), the number of breaths among which a significant correlation was found (lag), and the autocorrelation coefficient between one breath and the following one. Five patients were excluded because of nonstationarity of the data, leaving 46 cases for analysis. Between-group comparison was conducted with the Mann-Whitney test, and a nonparametric classification and regression tree was used to identify variables discriminating “success” (n = 32) and “failure” patients (n = 14). All coefficients of variation were significantly higher in success patients, who also exhibited significantly less respiratory autocorrelation (shorter “short memory”). The classification and regression tree analysis allocated all success patients to a group defined by a coefficient of variation of tidal volume/inspiratory time of ≥19% and a coefficient of variation of inspiratory time/respiratory period of ≥10% that did not contain any failure patient. All failure patients belonged to a group with coefficient of variation of tidal volume/inspiratory time of <19%, a lag tidal volume of ≥11, and that contained no success patient. Conclusions:In intensive care unit patients undergoing a spontaneous breathing trial, breathing variability is greater in patients successfully separated from the ventilator and the endotracheal tube. Variability indices are sufficient to separate success from failure cases.

Clinically relevant diaphragmatic dysfunction after cardiac operations

RATIONALE Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans. OBJECTIVES To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission. METHODS Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). MEASUREMENTS AND MAIN RESULTS Eighty-five consecutive patients aged 62 (54-75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44-68]). On Day 1, Ptr,stim was 8.2 (5.9-12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, -3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, -0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3-13.8] vs. 7.3 [5.5-9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3-13.5] vs. 7.8 [5.5-10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar. CONCLUSIONS A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00786526).

A method for studying the static volume-pressure curves of the respiratory system during mechanical ventilation

BACKGROUND Parkinsons disease (PD) is associated with sleep disorders and daytime sleepiness. Upper airway dysfunction in PD may promote obstructive sleep apnea. However, the frequency and clinical relevance of sleep-disordered breathing in PD remains unclear. METHODS Sleep apnea symptoms, cardiovascular events and treatment were collected in 100 patients with PD (50 unselected, consecutive patients matched for age, sex and body mass index with 50 patients referred for sleepiness) and 50 in-hospital controls. The motor and cognitive status was evaluated in patients with PD. The 150 subjects underwent a video-polysomnography. RESULTS Sleep apnea (defined as an apnea-hypopnea index greater than 5) was less frequent in the PD group (27% patients, including 6% with mild, 11% with moderate and 10% with severe sleep apnea) than in the control group (40% in-hospital controls, p<0.002). Sleep apnea was not associated with increased sleepiness, nocturia, depression, cognitive impairment and cardiovascular events in patients with PD. Sleep apnea was more frequent and severe in the most disabled patients. Patients with PD did not display sleep hypoventilation, stridor and abnormal central sleep apnea. In patients with REM sleep behavior disorders, snoring and obstructive sleep apnea occurred during REM sleep, although the chin muscle tone was maintained. CONCLUSION Obstructive sleep apnea does not seem to be a clinically relevant issue in PD. Daytime sleepiness, nocturia and cognitive impairment are mostly caused by other, non-apneic mechanisms. The maintenance of chin muscle tone during REM sleep behavior disorder has no influence on the frequency of apneic events.

Neurally Adjusted Ventilatory Assist Increases Respiratory Variability and Complexity in Acute Respiratory Failure

Phrenic nerve injury and diaphragmatic dysfunction can be induced by cardiac operation. The clinical consequences are not well-established. We evaluated 13 consecutive patients over a 2-year period with unexplained and prolonged difficulties in weaning from mechanical ventilation. The mean time of measurement from the operation day was 31 +/- 19 days (range 8 to 78). With the same technique we also evaluated 12 control patients: four patients at day 1 after cardiac operation while they were still intubated; four normally convalescing patients at day 7 or 8 after cardiac operation; and four patients who required prolonged mechanical ventilation because of another identified cause after cardiac operation. Diaphragmatic function was evaluated at the bedside from esophageal and gastric pressure measurements. A low or negative ratio of gastric pressure swing to transdiaphragmatic pressure swing, indicative of diaphragm dysfunction, was found in all 13 patients (mean -0.39 +/- 0.64). The difference between the 13 patients and all control groups was found to be highly significant. Transdiaphragmatic pressure measured during a maximal voluntary inspiratory effort and transdiaphragmatic pressure measured during a short, sharp sniff were markedly diminished (28 +/- 18 cm H2O and 13 +/- 15 cm H2O, respectively) in the 13 patients, significantly different from values in the four control patients studied at day 7 or 8. Transdiaphragmatic pressure measured after magnetic stimulation in four patients was also markedly reduced (7 +/- 5 cm H2O) as compared with normal theoretic values. Aminophylline infusion had no effect on any of these parameters. In one of two patients evaluated a second time, about 5 weeks later, a marked improvement was observed. Estimating the prevalence of clinically relevant diaphragmatic dysfunction, we found it to be 0.5% when no topical cooling was used and 2.1% when iced slush with no insulation pad was added for myocardial protection (p < 0.005). The most striking finding was that the clinical course of the 13 patients was marked by severe intercurrent events, including cardiorespiratory arrest after early tracheal extubation in 5 patients, nosocomial pneumonia in 11, prolonged mechanical ventilation in all (58 +/- 41 days), and a fatal outcome in 3. We conclude that prolonged postoperative diaphragmatic dysfunction may cause severe life-threatening complications after cardiac operation and can be limited to some extent by avoiding the use of iced slush topical cooling of the heart.

Baclofen therapy for chronic hiccup.

Abstract We describe a non-invasive method for measurement of the static volume-pressure curves of the respiratory system in mechanically ventilated patients. The method does not require disconnection of the patient from the ventilator. Using this technique, the measurements are obtained at a standardized volume history and are not affected by changes in lung volume due to continuing gas exchange, as is the case for the conventional “super-syringe” method. The measurements are made with the Siemens Servo Ventilator 9000 (Siemens, Solna, Sweden), which is provided with built-in sensors for flow and pressure, as well as with end-inspiratory and end-expiratory airway occlusion devices. The only additional equipment needed is a recorder or a computer system for data aquisition. The latter can be used to obtain volume by integration of the flow signals. If a recorder is used, an integrator is needed to obtain volume changes.