Stimulus parameters for phrenic nerve pacing in infants and children

Phrenic nerve pacing has been used since 1966 to support breathing in quadriplegics and patients with central hypoventilation syndrome (CHS). Recently, using low-frequency, long-inspiratory-time (T_i) stimulation, phrenic nerve pacing has been used successfully to support breathing 24 hours per day in adults and older children. However, no similar experience exists for infants and young children. Therefore, in 27 studies in 14 infants and children we determined the effects of changing T_i and interpulse interval (the inverse of stimulus frequency) on ventilation. Diaphragmatic action potentials, airflow, tidal volume, P_ACO2 and Sa_O2 were measured during sleep. Phrenic nerve pacing proved useful in 13 of 14 patients to support breathing either during wakefulness (n = 7) or during sleep (n = 6). We found that adequate ventilation could be achieved at significantly longer interpulse intervals, 95 ± 25 (mean ± SD) ms, and shorter T_i, 580 ± 80 ms, than previously reported. At an average respiratory rate of 21 ± 8 breaths/min it was thus possible to maintain adequate ventilation despite a marked reduction in the number of phrenic nerve stimuli. Theoretically, these reductions in phrenic nerve stimulation should minimize the chance of pacing-induced diaphragmatic damage. These results suggest that 24 hour per day phrenic nerve pacing may be a realistic goal in selected infants and children.     

High-frequency ventilation by bilateral phrenic nerve stimulation in dogs

We succeeded in achieving good gas exchange by oscillatory phrenic nerve stimulation (PNS) in dogs. In 7 out of 14 dogs, adequate gas exchange was attained by PNS at 3, 4 and 5 pulses per sec (pps). VE increased with stimulation frequency up to 4 or 5 pps, but decreased above 6 pps. We also applied sinusoidal oscillation using a piston pump at the trachea in the same dogs to analyze the mechanical properties of the respiratory system. The V/P ratio, oscillatory volume divided by driving pressure, decreased markedly at 6 Hz while the pleural pressure remained constant up to 10 Hz. These facts indicate that the fall in VE is due to mechanical properties of the airway and lung, and not due to failure of the ventilatory pump system. We conclude that frequencies of 3-5 pps in high-frequency ventilation are optimal for maintaining effective gas transport when the diaphragma is used as the oscillatory generator.     

Insidious phrenic nerve involvement in postpolio syndrome

A 49-year-old woman with amyotrophic sequelae of poliomyelitis experienced progressive left upper limb weakness and breathing discomfort while walking that had developed over one year prior to presentation. She had flaccid quadriplegia which was more marked in the left upper limb, with the C4- and C5-innervated muscles being most severely affected. Chest radiographs double exposed at maximal inspiration and expiration revealed poor respiratory movements in the left hemidiaphragm. Phrenic nerve conduction study demonstrated conspicuous diaphragmatic paralysis on the left side. The electrophysiological study supports radiological findings and provides useful evidence for insidious phrenic nerve involvement in postpolio syndrome.     

Cardiac pacing in a patient with diaphragm pacing for congenital central hypoventilation syndrome (Ondine's curse)

Mechanical ventilation support and diaphragm pacing has improved the prognosis of patients with idiopathic congenital central hypoventilation syndrome (CCHS; Ondine's curse). However, severe bradyarrhythmias may occur. This report is about a patient who was supplied with a bilateral diaphragm pacing system at early childhood. At the age of 17 years, he experienced multiple syncopes due to sinus nodal arrest, which was successfully treated by the implantation of a dual chamber pacemaker.     

Alveolar hypoventilation syndrome. Studies of ventilatory control in patients selected for diaphragm pacing

The syndrome of nocturnal hypoventilation and/or apnea without major intrinsic lung disease is of greater surgical interest since the introduction of therapeutic diaphragm pacing. Of our 29 patients successfully managed by diaphragm pacing, we describe 17 in whom detailed studies of the ventilatory responses to hypoxia are available.The diagnosis was established by the following criteria: (1) an increase in arterial carbon dioxide tension (PaCO₂) (> 45 mm Hg) and a depression in the arterial oxygen tension (PaO₂) (< 75 mm Hg) at least during sleep; (2) respiratory arrests and/or apneic episodes during sleep; (3) near normal tests of ventilatory capacity; and (4) diminished ventilatory response to carbon dioxide breathing.New information on the ventilatory responses to hypoxia was obtained by a nonsteady state closed-circuit rebreathing method. The following were compared: (1) hypoxia with carbon dioxide variably absorbed so as to maintain base line PaCO₂ (“normo”-capnic hypoxia); (2) 50 per cent oxygen with carbon dioxide accumulation (hypercapnia hyperoxia); and (3) carbon dioxide accumulation in room air (hypercapnic hypoxia). The data indicate (1) 15 patients showed no measurable ventilatory response to “normo”-capnic hypoxia and two patients showed blunted responses; (2) seven patients showed no ventilatory responses to carbon dioxide whereas 10 patients showed suboptimal increases; (3) combined hypoxia and hypercapnia caused a suboptimal ventilatory response in four patients. These same four patients showed blunted as opposed to absent ventilatory responses to carbon dioxide. (4) Five patients showed no ventilatory responses to all combinations.These 17 patients together with three others not so extensively studied have been managed by nocturnal diaphragm pacing for periods of four months to nearly eight years.We conclude (1) ablation or severe blunting of the ventilatory responses to hypoxia is a frequent and previously underestimated component of this disorder; and (2) diaphragm pacing is an appropriate form of therapy.     

房颤冷冻消融中右侧膈神经稳定起搏的方法探讨

目的右侧膈神经麻痹是冷冻球囊消融治疗房颤时最常见并发症。消融时监测膈神经活动是预防该并发症的有效措施。本研究通过测量上腔静脉区域起搏阈值和不同部位起搏的膈肌复合运动动作电位的方法,探讨膈神经的影像学的最佳起搏部位。方法前瞻性入选了32例接受冷冻球囊治疗的房颤患者。将可调弯标测电极导管以倒"U"字形放置到上腔静脉区域,使导管头端指向上腔静脉游离壁侧,右前斜造影判断上腔静脉形态,以及前壁、游离壁和后壁三个位点,将胸锁关节下第一、第二和第三椎间隙分别定义为上腔静脉区域的上、中、下三段。在各部位予以膈神经起搏(固定脉宽2 ms、起搏周长1 000 ms),通过改良的Ⅰ导联监测起搏膈神经时膈肌复合运动动作电位。检测各部位起搏阈值和各部位起搏输出5 m A时,膈肌复合运动动作电位的大小。结果采用倒"U"字形放置膈神经起搏导管可以达到稳定起搏。在32例患者中没有患者出现持续性膈神经麻痹。起搏位点共285个。可以发生膈神经夺获的位点占61.4%(175/285)。游离壁、后壁能够发生膈神经夺获的起搏位点显著多于前壁[游离壁为80.0%(76/95)、后壁为84.2%(80/95)、前壁为20.0%(19/95),P<0.001]。改良Ⅰ导联记录的后壁和游离壁起搏能够记录到膈肌复合运动动作电位的起搏点显著多于前壁起搏点(P<0.001)。膈神经起搏阈值和膈肌复合运动动作电位存在负相关性(r=-0.267,P=0.005)。结论通过倒"U"字形放置起搏导管于上腔静脉的后壁和游离壁,可以达到稳定的膈神经起搏。在起搏阈值最低的部位进行起搏可以展现更加清晰的膈肌复合运动动作电位,有助于冷冻消融时监测膈神经麻痹的发生。     

Clinical experience with transvenous atrial pacing.

Twelve patients were paced with a transvenous J-shaped bipolar electrode positioned in the right atrial appendage. All had chronic sinoatrial dysfunction and 5 had paroxysmal atrial arrhythmia: 2 had recent myocardial infarction, 1 angina decubitus, and 1 ventricular pre-excitation. Atrioventricular sequential pacing was employed in this last patient and this mode of pacing was substituted for atrial pacing in one other. The remaining 10 patients were paced from the atrium only. Electrode displacement occurred in 2 patients and 2 others had a rise in pacing threshold. After repositioning the electrode or substituting a more powerful pacemaker, sustained atrial capture was achieved in 3 of these 4. Sensing of spontaneous P waves was present constantly in 4 and variably in 3 of 9 patients. Symptomatic improvement was obtained in 10 patients. A bipolar pacemaker with a variable output voltage and a relatively high demand sensitivity is optimal for atrial pacing. Measurements of intra-atrial voltage with various electrode configurations in 7 patients suggest that atrial sensing may more often be achieved when the reference electrode is situated in the upper part of the right atrium than when it is close to the electrode tip in the atrial appendage.     

Properties of postganglionic sympathetic neurons with axons in phrenic nerve.

The aim of the study was to test the reflex and resting properties of postganglionic sympathetic neurons with axons located in the right phrenic nerve. The experiments have been performed on chloralose-anesthetized cats with both vago-aortic nerves cut. The somata or the postganglionic sympathetic neurons were located in the stellate ganglion. Axons of these neurons passed through the upper and lower phrenic nerve roots and through the phrenic nerve itself. The presence of cardiac and respiratory rhythmicities was detected in the activity of the phrenic postganglionic sympathetic neurons. Hyperventilation, which abolished burst discharges of the phrenic nerve, decreased the sympathetic activity by 14%. Systemic hypoxia (ventilating the animals for 2 min with 8% O2 in N2) increased the sympathetic activity threefold. The results of our experiments suggest that axons of the sympathetic neurons located in the right phrenic nerve could possibly be diaphragmatic muscle vasoconstrictors.     

Long-term experience with AutoCapture-controlled epicardial pacing in children.

AIMS: To examine the feasibility and safety of AutoCapture (AC)-controlled pacing with epicardial leads in children, and study the effects on device longevity. METHODS: A total of 62 children were prospectively enrolled. Pre-discharge testing precluded AC function in six children. In 56 (90%) children, devices with AC-controlled pacing were followed up to 9years. Calculated battery life in AC-controlled pacing was compared with theoretical calculations, using a two-fold stimulation output of measured thresholds. RESULTS: In 53 of 56 children, no differences were observed for evoked response signals (13.3 vs. 11.5mV, P = 0.20) or lead polarization safety margins (5.5 vs. 4.1, P = 0.25) at 6-month and 4-year follow-up. A crossover to conventional pacing was required in 3 of 56 children. AC-controlled pacing prolonged the calculated battery life up to 15% for the identity and integrity devices with 0.95A h capacity, compared with theoretical conventional settings (P = 0.008). In patients with ventricular pacing thresholds >1.5V at 0.5ms, battery life was increased by 30% compared with theoretical conventional settings (P < 0.001). CONCLUSION: AC-controlled pacing with epicardial leads is feasible and safe in children during long-term follow-up. An adequate lead polarization safety margin persists in most patients. Calculated battery life was prolonged up to 15% with AC-controlled pacing. Patients with high or fluctuating pacing thresholds benefit the most.     

Sepsis induces early phrenic nerve neuropathy in rats.

The aim of the present study was to investigate the electrophysiology of the phrenic nerve and the diaphragm muscle during sepsis. In total, 26 rats underwent either sham laparotomy or caecal ligation and puncture (CLP). Electrophysiology was evaluated via a phrenic nerve conduction study and needle electromyography of the diaphragm, prior to CLP, 6 and 24 h post-CLP and on day 7. The histopathology of the diaphragm muscle and phrenic nerve was also examined on day 7. In the sepsis group, the phrenic nerve conduction study showed decreased amplitude of compound action potential (CMAP), and prolongation in the duration and the latency of CMAP. The diaphragmatic needle electromyography showed decreased amplitude and frequency of the motor unit action potential (MUP), and prolongation in the duration of MUP, at all time points, compared with the pre-CLP values. The electrophysiological abnormalities were consistent with axonal and demyelinating phrenic nerve neuropathy. Electrophysiological abnormalities were present at 6 h with worsening at 24 h and on day 7. Histopathological examination showed normal muscular fibres and focally slight myelin degenerations of the phrenic nerve fibres. In conclusion, sepsis induced phrenic nerve neuropathy as early as the 6th h in rats.     

Cough in children with congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS) is defined as failure of the chemical (autonomic) control of breathing causing alveolar hypoventilation in the absence of pulmonary, cardiac, neuromuscular or patent brainstem lesions. Hypoventilation is predominant in non-rapid-eye-movement sleep, during which breathing is primarily under chemical control. Failure of the central integration of chemosensory inputs is proposed as the putative defect. A genetic basis for CCHS is supported by lines of evidence. In some diseases of the central nervous system there is more or less complete depression of the cough reflex, whereas spontaneous ventilation is generally preserved. Little is known regarding cough in CCHS patients. Parents consistently report that their children cough 'normally' during airway infections; in contrast, experimental lines of evidence suggest that CCHS children lack a cough response following inhalation of a tussigenic agent. Although several factors may account for the discrepancy, the possibility of a weakened or even absent cough reflex remains to be fully ascertained. Conceivably, a defective cough reflex, in conjunction with the well established lack of perception of respiratory discomfort, might result in an increased risk of potentially serious respiratory complications in CCHS patients.     

Late-onset central hypoventilation syndrome: a family genetic study.

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.     

Effect of bipolar electrode spacing on phrenic nerve stimulation and left ventricular pacing thresholds: an acute canine study

Background- Phrenic nerve stimulation (PNS) is a common complication of cardiac resynchronization therapy when left ventricular (LV) pacing occurs via a coronary vein. The purpose of this study was to evaluate the effects of bipolar electrode spacing on PNS and LV pacing thresholds. Methods and Results- Electrophysiology catheters with standard (2 mm-5 mm-2 mm) or modified (1 mm-5 mm-1 mm) interelectrode spacing was, respectively, inserted in a posterior/lateral cardiac vein in a randomized order in 6 anesthetized dogs via jugular access. The phrenic nerve was dissected via a left minithoracotomy and repositioned over the vein as close as possible to one of the electrodes. The presence of PNS was verified (ie, PNS threshold <2 V at 0.5 ms in unipolar configuration). Bipolar pacing was delivered using the electrode closest to the phrenic nerve as the cathode, and multiple bipolar electrode spacing configurations were tested. During bipolar pacing, PNS threshold increased as bipolar electrode spacing was reduced (P<0.05), whereas LV pacing thresholds did not change significantly (P>0.05). Compared with a standard bipolar electrode spacing of 20 mm for LV leads, 1 and 2 mm bipolar electrode spacing resulted in a PNS threshold increase of 5.5±2.2 V (P=0.003) and 2.8±1.7 V (P<0.001), respectively. Similarly, PNS threshold increased by 6.5±3.7 V with 1 mm and by 3.8±1.9 V with 2 mm bipolar pacing (both P<0.001), compared with unipolar pacing. Conclusions- This study suggests that reducing LV bipolar electrode spacing from the standard 20 mm to 1 or 2 mm may significantly increase the PNS threshold without compromising LV pacing thresholds.     

Long-term clinical performance of AAI pacing in patients with sick sinus syndrome: a comparison with dual-chamber pacing.

AIMS: In this clinical study, we compared two groups of age-matched patients, AAI and DDD, to evaluate the clinical benefits of AAI pacing in patients with sick sinus syndrome (SSS) and normal atrioventricular (AV) conduction. METHODS AND RESULTS: Ninety-five patients with SSS implanted with AAI pacemakers were compared with 101 SSS patients implanted with DDD pacemakers. Mortality, chronic atrial fibrillation, lead survival rates, and reoperation rates were compared by Kaplan-Meier analysis. Eight AAI devices were switched to DDD due to high-degree (grade 2-3) AV block. The incidence of high-degree AV block was 1.104%/year, with a freedom rate of 88.6% at 10 years. There were no significant differences between the two groups in survival rates (87.8% in AAI vs. 93.4% in DDD at 10 years), freedom from atrial fibrillation (93.6% vs. 90.6%), or freedom from reoperation (71.3% vs. 76.3%). On the other hand, lead failure was twice as frequent in the DDD group than in the AAI group (relative risk=2.045, P=0.0382). CONCLUSION: AAI pacing, a simple system using a single lead and single-chamber pacemaker, can achieve a clinical outcome similar to that of the DDD mode in patients with SSS and normal AV conduction.     

Unilateral phrenic nerve paralysis in a patient with Wegener's granulomatosis

A 35-year-old male diagnosed with Wegener's granulomatosis (WG) in 1989 recently came to our hospital with the complaint of left lumbar pain. He was found to have left nephrolithiasis and left diaphragmatic elevation. Fluoroscopic study and electromyographic examination revealed findings compatible with unilateral phrenic paralysis. We could not detect any cause other than WG which could be responsible for the unilateral diaphragmatic paralysis. Although different types of lung involvement have been reported in WG, to our knowledge this is the first in which unilateral phrenic nerve paralysis and diaphragmatic elevation associated with WG have been diagnosed.     

Alveolar hypoventilation in the obese: the obesity-hypoventilation syndrome

The obesity-hypoventilation syndrome (or alveolar hypoventilation in the obese) is a new name for an old syndrome, Pickwickian syndrome. It is defined as chronic alveolar hypoventilation (PaO(2)<70 mmHg, PaCO(2) > 45 mmHg) in obese patient with a body mass index > 30 kg/m(2) who have no other respiratory disease explaining the gas anomalies. The large majority of obese subjects are not hypercapnic, even in case of severe obesity. There are three principal causes explaining alveolar hypoventilation in obese subjects: high cost of the work of respiration, dysfunction of the respiratory centers, repeated episodes of nocturnal obstructive apnea. The obesity-hypoventilation syndrome is generally found in males aged over 50 years. Exercise-induced breathlessness is a constant finding. Diagnosis is often made after an episode of severe respiratory failure. Associated diseases favored by obesity are frequent: diabetes, high blood pressure, heart disease. By definition, there is a hypoxemia-hypercapnia syndrome persisting after an acute episode. Spirography usually demonstrates moderate volume restriction. Pulmonary hypertension is frequent but not constant. Obesity-hypoventilation syndrome must be distinguished from obstructive sleep apnea, although the two conditions are often associated. Obstructive sleep apnea may be absent in certain patients with obesity-hypoventilation syndrome (we have had several cases) and inversely, obesity is not observed in certain patients with obstructive apnea. It should be recalled that the term Pickwickian syndrome designates obesity-hypoventilation syndrome (with or without obstructive apnea) and not obstructive sleep apnea syndrome.