Some references about evolution of phrenic nerve stimulation for electroventilation

Conventional monopolar stimulation concept

In 1966 Glenn’s group in Yale University had changed their inductively fed cardiac pacer into a diaphragm pacer (DP) for treatment of central apnea 1.Inductive powering of implanted stimulators avoids the side effects of prior methods that used transcutaneous nerve stimulation, also the possible side effects of skin penetrating wires are eliminated as such skin penetrating wires are not needed. Electrically induced muscle fatigue was an obstacle for full-time diaphragm pacing when monopolar stimulation was utilized 2 ; about one third of 37 patients managed with DP alone, one third needed MV for half of a day, one third could use DP for several hours only.

1976 Salmons published on the dependence of muscle types on the frequency of their controlling nerve 3. Glenn (1984) and Elefteriades (2002) successfully adopted this finding for patients using the DP 4,5; after a “conditioning period” of several month’s their diaphragm muscle had changed into a slow-twitch fatigue-resistant muscle. Electrically induced muscle fatigue specific for monopolar phrenic nerve stimulation was in better control but still having limiting features.

Sequential, multipolar stimulation concept utilized in Atrostim PNS

In the eighties Talonen introduced sequential 4-pole phrenic nerve stimulation for electroventilation 6,7,8 ; the conditioning period shrunk from months to weeks 9,10 since muscle type transformation was no longer needed to reach fatigue-free diaphragm contraction. The potential of this stimulation concept to reduce muscle fatigue was earlier proved in direct skeletal muscle stimulation by Peckham 11.

Modern electroventilation using inductively fed and controlled implanted stimulators are now commercially available since more than 40 and 20 years 12,13,14. During the whole period of inductively fed electroventilation, including the experimental period for both devices (starting 1966 and 1981, respectively), no death occurred because of malfunction of a devices; this is now experience from about 2000 cases 15.

Compared to conventional mechanical ventilation, the higher investment is paid off after one year of use 10 ; this is because of large savings due to reduced infection frequency and reduced need of single use equipment 10 and nursing time for airway cleaning 10.

The positive influence of PNS on patients’ quality of life is obvious 17,18,19,20 and measureable: on the spinal cord injured independence measure 21 the change from mechanical ventilation (3 points) to PNS (11 points) improves quality of life almost four times.


1.       Heeckeren,van D.W.; Glenn,W.W.L. Electrophrenic respiration by radiofrequency induction. J Thoracic Cardiovasc Surg 1966;52:655-65
2.       Glenn,W.W.L; Holcomb,W.G; Shaw,R.K; Hogan,J.F; Holschuh,K.R. Long-term ventilatory support by diaphragm pacing in quadriplegia. AnnSurg1976;183(5):566-76
3.       Salmons,S; Sreter,F.A. Significance of impulse activity in the transformation of skeletal muscle type. Nature 1976;263(5572):30-4
4.       Glenn,W.W.L; Hogan,J.F; Loke,J.S.O; Ciesielski,T.E; Phelps,M.L; Rowedder,R. Ventilatory support by pacing of the conditioned diaphragm in quadriplegia. N Engl J Med 1984;310:1150-5
5.       Elefteriades,J.A.; Quin,J.A.; Hogan,J.F.; Holcomb,W.G.; Letsou,G.V.; Chlosta,W.F.; Glenn,W.W.W.L. Long-term follow-up of pacing of the conditioned diaphragm in quadriplegia. PACE 2002;26(6):897-906
6.       Talonen,P.; Baer.G.; Huhti,M.; Häkkinen,V. Modulation of muscle force by recruitment and firing rate during multipolar nerve stimulation. in: Life support systems – The journal of the European Society for Artificial Organs. Proceedings, Annual Meeting ESAO, Athens Greece 1985; Vol. 3; Suppl. 1:316-320
7.       Talonen,P.P.; Baer,G.A.; Hakkinen,V.; Ojala,J.K. Neurophysiological and technical considerations for the design of an implantable phrenic nerve stimulator. Medical & Biological Engineering & Computing 1990;28(1):31-7
8.       Baer,G.A.; Talonen,P.P.; Shneerson,J.M.; Markkula,H.; Exner,G.; Wells,F.C. Phrenic nerve stimulation for central ventilatory failure with bipolar and four-pole electrode systems. Pacing & Clinical Electrophysiology 1990;13(8):1061-72
9.       Baer,G.A.; Talonen,P.P.; Hakkinen,V.; Exner,G.; Yrjola,H. Phrenic nerve stimulation in tetraplegia. A new regimen to condition the diaphragm for full-time respiration. Scand J Rehabil.Med. 1990;22(2):107-11
10.    Hirschfeld,S.; Exner,G.; Luukkaala,T.; Baer,G.A. Mechanical ventilation or phrenic nerve stimulation for treatment of spinal cord injury-induced respiratory insufficiency. Spinal Cord 2008;46(11):738-42
11.    Peckham,P.H.; Van der Meulen,J.P.; Reswick,J.B. Electrical activation of skeletal muscle by sequential stimulation. in: Wulfson,N. and Sances Jr.,A. (eds) The Nervous System and Electrical Currents, Vol. 1:45-50, New York: Plenum, 1970. ISBN 0-306-30478-3
12.    Weese-Mayer,D.E; Morrow,A.S.; Brouillette,R.T.; Ilbawi,M.N.; Hunt,C.E. Diaphragm pacing in infants and children. A life-table analysis of implanted components. Am Rev Respir Dis 1989;139(4):974-9
13.    Weese-Mayer,D.E.; Silvestri,J.M.; Kenny,A.S.; Ilbawi,M.N.; Hauptman,S.A.; Lipton,J.W.; Talonen,P.P.; Garcia,H.G.; Watt,J.W.; Exner,G.; Baer,G.A.; Elefteriades,J.A.; Peruzzi,W.T.; Alex,C.G.; Harlid,R.; Vincken,W.; Davis,G.M.; Decramer,M.; Kuenzle,C.; Saeterhaug,A.; Schober,J.G. Diaphragm pacing with a quadripolar phrenic nerve electrode: an international study. Am Rev Respir Dis 1996;19(9):1311-19
14.    Le Pimpec-Barthes, F.; Gonzalez-Bermejo, J.; Hubsch, J-P.; Duguet, A.; Morélot-Panzini, C.; Riquet, M.; Similowski, T. Intrathoracic phrenic pacing: A 10-year experience in France. J. Thor. Cardiovasc. Surg. 2008;142(2):378-383
15.    Creasey,G.; Elefteriades,J.; DiMarco,A.; Talonen,P.; Bijak,M.; Girsch,W.; Kantor,C. Electrical stimulation to restore respiration. J Rehabil.Res Dev. 1996;33(2):123-32
16.    Luetjens,A; Baer ,G.A. Consumption of single use equipment for treatment of SCI-induced respiratory insufficiency using mechanical ventilation (MV) or phrenic nerve stimulation (PNS). IsCoS2008, Durban, Z.A., abstr.35
17.    Carter,R.E; Donovan,W.H; Halstead,L; Wilkerson,M.A. Comparative study of electrophrenic nerve stimulation and mechanical ventilatory support in traumatic spinal cord injury. Paraplegia 1987;25:86-91
18.    Esclarin,A..; Bravo,P.; Arroyo,O.; Mazaira,J.; Garrido,H..; Alcaraz,M..A.. Tracheostomy versus diaphragmatic pacemaker ventilation in high spinal cord injury. Paraplegia 1994;32(10):687-93
19.    Adler,D.; Gonzalez-Bermejo,J.; Duguet,A.; Demoule,A.; Le Pimpec-Barthes,F.; Hurbault,A.; Morelot-Panzini,C.; Similowski,T. Diaphragm pacing restores olfaction in tetraplegia. Eur.Respir.J. 2009;34(2):365-70
20.    Romero-Ganuza,F.J.; Gambarrutta-Malfatti,C.; Diez de la Lastra-Buigues; Marin-Ruiz,M.A.; Merlo-Gonzalez,V.E.; Sanchez-Aranzueque Pantoja,A.M.; Garcia-Moreno,F.J.; Mazaira-Alvarez,J. [Diaphragmatic pacemaker as an alternative to mechanical ventilation in patients with cervical spinal injury]. Med.Intensiva. 2011;35(1):13-21
21.    Catz,A.; Itzkovich,M.; Tesio,L.; Biering-Sorensen,F.; Weeks,C.; Laramee,M.T.; Craven,B.C.; Tonack,M.; Hitzig,S.L.; Glaser,E.; Zeilig,G.; Aito,S.; Scivoletto,G.; Mecci,M.; Chadwick,R.J.; El Masry,W.S.; Osman,A.; Glass,C.A.; Silva,P.; Soni,B.M.; Gardner,B.P.; Savic,G.; Bergstrom,E.M.; Bluvshtein,V.; Ronen,J. A multicenter international study on the Spinal Cord Independence Measure, version III: Rasch psychometric validation. Spinal Cord 2007;45(4):275-91


Share this page

Share this page in Facebook Send link