Robert Schilz

Amyotrophic lateral sclerosis: the Midwestern surgical experience with the diaphragm pacing stimulation system shows that general anesthesia can be safely performed

BACKGROUNDnThere is a paucity of literature concerning general anesthesia and surgery in patients with amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease). This report summarizes the largest series of surgical cases in ALS during multicenter prospective trials of the laparoscopic diaphragm pacing system (DPS) to delay respiratory failure.nnnMETHODnThe overall strategy outlined includes the use of rapidly reversible short-acting analgesic and amnestic agents with no neuromuscular relaxants.nnnRESULTSnFifty-one patients were implanted from March 2005 to March 2008 at 2 sites. Age at implantation ranged from 42 to 73 years and the percent predicted forced vital capacity (FVC) ranged from 20% to 87%. On preoperative blood gases, Pco(2) was as high as 60. Using this protocol, there were no failures to extubate or 30-day mortalities. The DPS system increases the respiratory system compliance by decreasing posterior lobe atelectasis and can stimulate respirations at the end of each case.nnnCONCLUSIONSnLaparoscopic surgery with general anesthesia can be safely performed in patients with ALS undergoing DPS.

Final analysis of the pilot trial of diaphragm pacing in amyotrophic lateral sclerosis with long-term follow-up: Diaphragm pacing positively affects diaphragm respiration

BACKGROUNDnRespiratory insufficiency is the major cause of mortality in patients with amyotrophic lateral sclerosis or Lou Gehrigs disease. This is the final report of the diaphragm pacing (DP) pilot trial.nnnMETHODSnPatients underwent laparoscopic diaphragm electrode implantations and subsequent conditioning of diaphragms. Serial respiratory function tests were performed in the initial year and followed until death.nnnRESULTSnSixteen patients were implanted with no perioperative or unanticipated device-related adverse events. There were 452 implant-months of follow-up. DP allowed greater movement of the diaphragm under fluoroscopy, increased muscle thickness, and decreased the decline in forced vital capacity. Median survival from implant was 19.7 months with the cause of death respiratory in only 31%.nnnCONCLUSIONSnLong-term analysis of DP in amyotrophic lateral sclerosis showed no safety issues and can positively influence diaphragm physiology and survival. This formed the initial basis for subsequent US Food and Drug Administration approval.

Extended use of diaphragm pacing in patients with unilateral or bilateral diaphragm dysfunction: A new therapeutic option

BACKGROUNDnDiaphragm dysfunction (DD) can cause sleep abnormalities, dyspnea, atelectasis, and respiratory failure. Historical treatments, including positive pressure ventilation or diaphragm plication, may alleviate symptoms but do not restore physiologic diaphragm function. Diaphragm pacing (DP) is approved for spinal cord-injured patients and in amyotrophic lateral sclerosis. We report a series of DD patients undergoing use of DP outside of these initial indications.nnnMETHODSnThis report involves a prospective, nonrandomized, interventional trial under institutional review board approval at a single institution. DP involves laparoscopic motor point mapping with implantation of intramuscular electrodes in each hemidiaphragm. Postoperatively, diaphragm conditioning ensues.nnnRESULTSnTwenty-seven patients were evaluated; all patients had symptomatic and objective hypoventilation for an average of 36xa0months of symptoms. Causes included idiopathic (nxa0=xa013), chest surgery (nxa0=xa05), shoulder surgery or trauma (nxa0=xa06), and others (nxa0=xa03); 17 had bilateral involvement, 6 had nonstimulable diaphragms and were not implanted, and 21 were implanted. Thirteen (62%) had substantial clinically relevant respiratory improvements. Four ventilator patients were weaned completely. Four had partial improvement, 3 had no improvement, and 1 patient was lost to follow-up for objective analysis.nnnCONCLUSIONnThis is the first report of DP being used to treat diverse causes of DD. Eighty-one percent of implanted patients experienced improvements. This success suggests a potential for a wider use of DP and areas for future research.

Identification of unexpected respiratory abnormalities in patients with amyotrophic lateral sclerosis through electromyographic analysis using intramuscular electrodes implanted for therapeutic diaphragmatic pacing

BACKGROUNDnAmyotrophic lateral sclerosis patients have significant respiratory abnormalities with incomplete understanding of respiratory control. This study analyzes electromyography (EMG) of the diaphragm (dEMG) using implanted diaphragm pacing (DP) electrodes.nnnMETHODSnRetrospective analysis of dEMG data were obtained during Institutional Review Board and US Food and Drug Administration approved trials. The electrodes were used to analyze epochs of dEMG during multiple respiratory cycles.nnnRESULTSnFifty-three patients were implanted. Thirty-six had bilateral dEMG assessments, 18 had continuous overnight readings with pulse oximetry, and 19 had serial analysis. Several findings revealed an alteration in the central respiratory drive including central apnea, hypoventilation, and hypercarbia. The electrodes showed unilateral dysfunction and demonstrated noninvasive ventilation suppression of diaphragm activity. DP can be used for serial monitoring, to decrease hypercarbia, improve sleep, and decrease atrophy.nnnCONCLUSIONSnMultiple abnormalities of respiratory control can be seen in amyotrophic lateral sclerosis patients using dEMG through therapeutic DP electrodes. DP is used to overcome instability of respiratory control when there are intact diaphragm motor units leading to improved survival.

Completed FDA feasibility trial of surgically placed temporary diaphragm pacing electrodes: A promising option to prevent and treat respiratory failure

BACKGROUNDnEtiologies contributing to failure to wean from mechanical ventilation (MV) are multiple, resulting in morbid and costly outcomes. Diaphragm pacing (DP) is used in spinal cord injury to replace MV. Temporary DP could be utilized in acute respiratory failure to reduce MV.nnnMETHODSnA prospective FDA feasibility trial evaluated temporary DP electrodes implanted in each hemi-diaphragm during a subjects primary procedure. Objectives included: ability to provide ventilation, stability analysis with diaphragm electromyography, and adverse event monitoring.nnnRESULTSnTwelve patients underwent successful implantation via median sternotomy, laparoscopy or laparotomy. Electrode stimulation exceeded ideal tidal volumes by an average of 37% (0%-95%) confirming ability to prevent atrophy. Daily electromyography confirmed stability of placement and was useful in evaluating hypoventilation. There were no complications and all 48 study electrodes remained intact until complete removal.nnnCONCLUSIONnThis trial demonstrates ease of placement, removal, functionality and safety of temporary DP electrodes which therapeutically decreases diaphragm atrophy.

Long-term experience with diaphragm pacing for traumatic spinal cord injury: Early implantation should be considered

Background: Cervical spinal cord injury can result in catastrophic respiratory failure requiring mechanical ventilation with high morbidity, mortality, and cost. Diaphragm pacing was developed to replace/decrease mechanical ventilation. We report the largest long‐term results in traumatic cervical spinal cord injury. Methods: In this retrospective review of prospective institutional review board protocols, all patients underwent laparoscopic diaphragm mapping and implantation of electrodes for diaphragm strengthening and ventilator weaning. Results: From 2000 to 2017, 92 patients out of 486 diaphragm pacing implants met the criteria. The age at time of injury ranged from birth to 74 years (average: 27 years). Time on mechanical ventilation was an average of 47.5 months (range, 6 days to 25 years, median=1.58 years). Eighty‐eight percent of patients achieved the minimum of 4 hours of pacing. Fifty‐six patients (60.8%) used diaphragm pacing 24 hours a day. Five patients had full recovery of breathing with subsequent diaphragm pacing removal. Median survival was 22.2 years (95% confidence interval: 14.0–not reached) with only 31 deaths. Subgroup analysis revealed that earlier diaphragm pacing implantation leads to greater 24‐hour use of diaphragm pacing and no need for any mechanical ventilation. Conclusion: Diaphragm pacing can successfully decrease the need for mechanical ventilation in traumatic cervical spinal cord injury. Earlier implantation should be considered.

Selection of Infusion Prostacyclin Therapy in Pulmonary Arterial Hypertension: Not Just a Last Resort

Pulmonary arterial hypertension (PAH) is a progressive, fatal vasculopathy that clinically manifests as increased pulmonary vascular resistance and elevation of pulmonary arterial pressures, ultimately leading to right heart failure and death. Median untreated survival period is 2.8 years, with a survival rate of 34% at 5 years before the availability of epoprostenol.1 Parenteral prostacyclin therapy is arguably the most effective and longest Food and Drug Administration-approved class of drugs for PAH and has been included in guidelines for treatment of PAH for almost 20 years. Intravenous epoprostenol as Flolan® remains the only drug that has demonstrated a survival advantage (Figure 1).2 Despite this demonstration of survival advantage and early evidence in its ability to improve a majority (70%) of patients to a point where they no longer required active listing for lung transplantation,3 epoprostenol or other infusion agents have consistently been shown to be withheld or underutilized in patients wit...

Calcium Channel Blocker Therapy: When a Drug Works, it Works. When it Doesn't, it Doesn't

Calcium channel blocker (CCB) therapy continues to be an element of modern pulmonary arterial hypertension treatment guidelines. However, the true number of patients that can be effectively treated with CCBs is very small. It is important to remember that those who truly retain a long-term benefit are those that tend to have a dramatic initial response to vasodilators and will attain normal or near normal hemodynamics and functional class after starting CCBs. Should a patient do so, they may well enjoy dramatic long-term survival on this regimen. In this article we discuss details and experience with calcium channel antagonists.

Transgenic Animals and the Modelling of Asthma

The exact cellular and molecular events leading to airways obstruction and physiological dysregulation in asthma have not been fully defined through human experimentation in vivo. Significant genetic, pathophysiological and clinical variation in the presentation and natural history of asthma complicates this experimentation. Obvious economic and ethical concerns also limit the investigation of asthma in human subjects. Nevertheless, direct examination of specimens from asthmatics has led to an important shift in our concept of the pathogenesis of this disorder. It is now widely held that asthma is a chronic inflammatory disorder and that the obstruction and airways hyperresponsiveness (AHR) that are characteristic of asthma are largely the result of this inflammatory response and its fibrotic and tissue-damaging sequellae. As a result, anti-inflammatory interventions are now the cornerstone of asthma therapy and the inflammatory mechanisms of asthma are now the major focus of research activities in this field. In spite of this insight, the role that individual mediators play in asthmatic inflammation, the fundamental molecular mechanisms leading to the chronicity of asthmatic inflamation, and the events linking inflammation, bronchoconstriction and bronchial reactivity remain important, inadequately addressed areas in the pathogenesis of this disorders.