MONTREAL--A new method promises to improve the efficacy of mechanical ventilation and lessen its adverse effects by permitting the respiratory center in a patient's brain to control the ventilator. The method, known as neurally adjusted ventilatory assist, uses computer-assisted analysis of electrical activity in the diaphragm to adjust ventilatory assist both within a given breath and between breaths.

Preliminary data were reported by Sinderby et al[1] in Nature Medicine, and the method is now being tested in clinical trials. According to the international team of investigators, "[T]his represents the first form, to our knowledge, of assisted ventilation in which the patient's respiratory center can assume full control of the magnitude and timing of the mechanical support provided, regardless of changes in respiratory drive, mechanics, and muscle function."

In an interview with PULMONARY REVIEWS, lead study author Christer Sinderby, PhD, explained the process. "Neural control of mechanical ventilation can overcome problems that develop when current methods of adjusting and/or triggering partial ventilatory assist fail and, thus, sedation or paralysis of the patient becomes necessary. Neural control can improve patient-ventilator interaction and may make it possible to maintain spontaneous breathing in ventilator-dependent patients."

Neural control of respiration originates in the respiratory center, and signals are transmitted through the phrenic nerve to excite the diaphragm. This excitation produces contraction of the diaphragm; expansion of the chest wall and lung; and an increase in airway pressure, flow, and volume. Direct monitoring of the phrenic nerve is not possible, but the neural method monitors electrical signals to the diaphragm. These signals represent neural drive to the diaphragm and are a proxy for phrenic nerve activity.

Bipolar electrodes attached to a nasogastric tube are positioned in the esophagus at the level of and perpendicular to the crura of the diaphragm. The active muscle creates an electrically charged region around the electrode. The online monitoring system differentially amplifies signals from each electrode pair and digitizes them; the signals are then filtered to reduce the influence of cardiac electric activity, motion artifacts, and noise. The resulting signal can help monitor the patient's respiration or control the timing and/or levels of the ventilatory assist.

As respiratory needs increase and the respiratory center "asks" the diaphragm for more effort, the neurally controlled system increases the amount of help the ventilator supplies. The degree of ventilatory support varies on a moment-by-moment basis according to a mathematical formula that includes diaphragmatic electrical activity. "This allows the patient's respiratory center to be in direct control of the mechanical support provided throughout the course of each breath," according to the authors. Thus, "any variation in neural respiratory output [can] be matched by a corresponding change in ventilatory assistance."

In contrast, conventional methods for regulating ventilatory support use airway pressure, flow, or volume to initiate and regulate ventilatory assistance. These variables worsen with increasing respiratory dysfunction. Current methods also may not detect the beginning and/or end of the patient's effort to inhale, because of delays associated with respiratory dysfunction. The result is that by the time the ventilator kicks in, most of the patient's inspiratory effort has already been generated. Expiratory flow limitations can increase intrinsic positive end-expiratory pressure (PEEP), and intrinsic PEEP must be overcome before airway pressure can be lowered or flow generated to trigger the ventilator. External PEEP is sometimes applied to balance intrinsic PEEP; but this is an uncertain process, and excessive external PEEP can produce further hyperinflation. Intrinsic PEEP does not affect neural function.

Under neural triggering, the ventilator provides support as soon as diaphragmatic electrical activity exceeds a threshold level, and there is almost no delay between this trigger and the onset of inspiratory flow and increase in airway pressure. "Because of the coordination between diaphragmatic activation and ventilatory support throughout the breathing cycle, undue prolongation or premature interruption of mechanical assistance in relation to patient effort should be avoided," the researchers noted.

Use of the neural method requires that the respiratory center, phrenic nerve, and neuromuscular junction be functionally intact. It can be used with conventional, noninvasive, or negative-pressure ventilators.

The investigators hope the new method will improve patient-ventilator interaction and increase patient comfort. They also project that it will reduce the risk of iatrogenic hyperinflation, respiratory alkalosis, and hemodynamic impairment. They expect it to be most useful in patients with the most severe forms of respiratory impairment and in pediatric cases, in which better patient-ventilator synchrony may reduce the risk of pneumothorax and its associated risk of cerebral hemorrhage.

According to Dr. Sinderby, assistant professor at the Guy Bernier Research Center, Department of Medicine, University of Montreal, the technology for obtaining and processing the electrical activity of the diaphragm has been thoroughly validated. "We are currently in the process of performing clinical trials in which we compare the new technology to current technologies. So far, our experience with neural triggering of mechanical ventilation is very positive," he said. "The technology is being used in clinical research at the moment, and it needs to go through the standard steps of evaluation required by [the] FDA or equivalent agencies in other countries."

There is no estimation of cost at present. The training required for use of this method involves learning to position the electrode and to adjust the trigger and the level of ventilatory assist.

--Janis Kelly

Reference
1. Sinderby C, Navalesi P, Beck J, et al. Neural control of mechanical ventilation in respiratory failure. Nat Med. 1999;5:1433-1436.

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