ResearchIncreased duration of mechanical ventilation is associated with decreased diaphragmatic force : a prospective observational study

Introduction: Respiratory muscle weakness is an important risk factor for delayed weaning. Animal data show that mechanical ventilation itself can cause atrophy and weakness of the diaphragm, called ventilator-induced diaphragmatic dysfunction (VIDD). Transdiaphragmatic pressure after magnetic stimulation (TwPdi BAMPS) allows evaluation of diaphragm strength. We aimed to evaluate the repeatability of TwPdi BAMPS in critically ill, mechanically ventilated patients and to describe the relation between TwPdi and the duration of mechanical ventilation. Methods: This was a prospective observational study in critically ill and mechanically ventilated patients, admitted to the medical intensive care unit of a university hospital. Nineteen measurements were made in a total of 10 patients at various intervals after starting mechanical ventilation. In seven patients, measurements were made on two or more occasions, with a minimum interval of 24 hours. Results: The TwPdi was 11.5 ± 3.9 cm H2O (mean ± SD), indicating severe respiratory muscle weakness. The betweenoccasion coefficient of variation of TwPdi was 9.7%, comparable with data from healthy volunteers. Increasing duration of mechanical ventilation was associated with a logarithmic decline in TwPdi (R = 0.69; P = 0.038). This association was also found for cumulative time on pressure control (R = 0.71; P = 0.03) and pressure-support ventilation (P = 0.05; R = 0.66) separately, as well as for cumulative dose of propofol (R = 0.66; P = 0.05) and piritramide (R = 0.79; P = 0.01). Conclusions: Duration of mechanical ventilation is associated with a logarithmic decline in diaphragmatic force, which is compatible with the concept of VIDD. The observed decline may also be due to other potentially contributing factors such as sedatives/analgesics, sepsis, or others. Introduction Weaning from mechanical ventilation is an important and time-consuming process in critically ill patients. Weaning comprises approximately 40% of the time spent on the ventilator [1]. Although several factors may contribute to delayed weaning, a major determinant appears to be respiratory muscle weakness [2]. The most frequent causes of muscle weakness in critically ill patient, which may affect both limbs and respiratory muscles, are critical illness polyneuropathy and myopathy. Many potential risk factors hereof have been described in several prospective trials [3-9]. All of these studies, however, focused on peripheral muscle strength. Limited data are available specifically addressing the respiratory component of muscle weakness, suggesting septic shock to be a strong predictor [2]. Extensive animal data also suggest that controlled mechanical ventilation (CMV) itself, during which the diaphragm is inactive, may cause atrophy of the diaphragm and decreased force-generating capacity in vitro and in vivo [10-16]. This occurs in a time-dependent way, as early as 12 h after starting CMV [11]. This phenomenon has been called ventilator-induced diaphragmatic dysfunction (VIDD). Although CMV is not the preferred mode of ventilation in the ICU, it is necessary in particular situations, such as during the use of neuromuscular blockade, in attempts to minimize oxygen consumption, central neurologic problems, and so forth, and therefore still is used in the ICU [17]. If VIDD also occurs in * Correspondence: Greet.Hermans@uz.kuleuven.be 1 Medical Intensive Care Unit, General Internal Medicine, University Hospitals Leuven, Herestraat 49, B3000 Leuven, Belgium Full list of author information is available at the end of the article © 2010 Hermans et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hermans et al. Critical Care 2010, 14:R127 http://ccforum.com/content/14/4/R127 Page 2 of 10 humans, it may therefore have important clinical impact. Brain-dead patients undergoing mechanical ventilation for 18 to 69 h indeed showed atrophy of the diaphragm [18]. A reliable tool to measure respiratory muscle force is essential to guide further research concerning causes and consequences of respiratory muscle weakness and potential therapies aimed at preserving respiratory muscle force in critically ill patients. Recently, a method of measuring diaphragmatic force was introduced by Watson [19] in critically ill patients. This involves stimulation of both phrenic nerves at the anterior side of the neck by using two magnetic coils, called bilateral anterior magnetic phrenic nerve stimulation (BAMPS). The resulting diaphragmatic contraction is registered by using two balloon catheters positioned in the esophagus and stomach. Measuring twitch transdiaphragmatic pressure appeared feasible in critically ill patients, although not all patients can be measured. Critically ill patients had significantly lower diaphragmatic force compared with healthy controls. Later, the same technique was used by Laghi [20], who confirmed the reduced diaphragmatic force in patients ready to be weaned. The purpose of the present study was to evaluate the repeatability of BAMPS TwPdi on different occasions in critically ill and mechanically ventilated patients. We also aimed to examine whether TwPdi would decrease with increasing duration of mechanical ventilation. Materials and methods Patients Patients were eligible if they were admitted between March 2007 and October 2008 to the medical intensive care unit, which is a 17-bed ICU of a tertiary center with approximately 750 admissions yearly. Inclusion criteria consisted of intubation and mechanical ventilation, hemodynamic stability, and stable respiratory status with a positive end-expiratory pressure (PEEP) ≤7 cm H2O. Contraindications were those related to magnetic stimulation (pacemaker or implantable cardioverter-defibrillator, prosthetic valve, cervical implants, cervical trauma), contraindication for gastric/esophageal balloon placement (coagulation disorders, low platelet count, gastric or esophageal pathology), factors possibly interfering with correct pressure measurements (multiple-functioning chest drains, severe abdominal infections, recent major abdominal surgery, agitation, bronchospasm), age younger than 18 years, pregnancy, and having received neuromuscular blocking agents in the past 24 h. Mechanical ventilators used were Dräger, EvitaXL, and Dräger, Evita4. During mechanical ventilation, the need for analgesics and sedatives was daily evaluated and titrated by the treating physician to the minimum needed, aiming at a sedation agitation score [21] of 3 to 4. Informed consent was obtained from the patients or their relatives. The study was approved by the local ethics committee. Measurement of diaphragmatic force We measured twitch transdiaphragmatic pressure (TwPdi) by using bilateral anterior magnetic phrenic nerve stimulation (BAMPS), as described previously [19]. In brief, the phrenic nerves were stimulated bilaterally from the anterior approach, at the posterior border of the sternocleidomastoid muscle, at the level of the cricoids, by using two figure-of-eight 45-mm magnetic coils (Magstim, Dyfed, Wales) and a bistim (Magstim, Dyfed, Wales). A custom-built, two-way occlusion valve was used to create isometric conditions during stimulation. Esophageal and abdominal pressure changes were measured by using balloon catheters (UK Medical, Sheffield, UK) inserted through the nose after local anesthesia. The gastric balloons were filled with 2 ml of air, and the esophageal balloons contained 0.5 ml of air. To verify correct positioning of the abdominal catheter, abdominal compression was applied. The position of the esophageal catheter was confirmed to be correct if the end-expiratory pressure was near the PEEP level applied, and if inspiration against the closed airway resulted in similar pressure changes on the esophageal and tracheal tracings. Tracheal, abdominal (TwPabd), and esophageal pressures (TwPes) were measured by using Validyne MP45 transducers, 250 cm H2O, connected to a custom-built carrier amplifier. Tracheal pressure was measure at the proximal end of the endotracheal tube. Biopac MP150 (Cerom, Paris, France) was used as the data-acquisition system. Patients were left breathing quietly for 20 min after balloon placement. After determining the optimal position of the coils, at least three stimulations were performed at 100% of maximal output. To evaluate supramaximality, patients were also stimulated at 70%, 90%, and, if necessary, at 95%. All measurements were performed with the head end in 30-degree upward position. Between two stimulations, at least a 30-sec pause was obtained to avoid superposition. To evaluate repeatability of the measurement, if possible, patients were measured on two occasions as close together as technically feasible and according to the patients' clinical status, but with a minimal time interval of 24 h. Analysis of signals Individual abdominal and esophageal pressure signals were accepted for analysis if they were timed at end expiration with no major cardiac artefact, if stable and physiologically acceptable end-expiratory pressure was present, and if active abdominal muscle contraction or esophageal contraction during the stimulation was absent. TwPes and Twabd were defined as the maximal Hermans et al. Critical Care 2010, 14:R127 http://ccforum.com/content/14/4/R127 Page 3 of 10 excursion of the esophageal and abdominal tracing, respectively, on stimulation from the value immediately before stimulation (Figure 1). TwPdi was calculated as the difference between TwPabd and TwPes. The mean value of at least three signals was made to determine TwPdi on a given occasion. Data analysis Mean values of TwPdi, TwPabd, and TwPes in the total case series were calculated by using the mean v