Long term Recovery in Critical Illness Myopathy is complete, contrary to Polyneuropathy Running head: Recovery in CIM and CIP
Susanne Koch1, MD; Tobias Wollersheim1, Jeffrey Bierbrauer1, MD; Kurt Haas1, Rudolf Mörgeli1, Maria Deja1, PhD; Claudia D. Spies1, PhD; Simone Spuler2, PhD; Martin Krebs1, MD; Steffen Weber-Carstens1, PhD 1
Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and
Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany 2
Muscle Research Unit, Experimental and Clinical Research Center, Charité-
Universitätsmedizin Berlin, Lindenberger Weg 80, 13125 Berlin, Germany
Corresponding author: Susanne Koch, MD Dept. of Anesthesiology and Intensive Care Medicine Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Mitte Augustenburger Platz 1 D-13353 Berlin, Germany Tel: +49 30 450651808 FAX: +49 30 551909 e-mail: [email protected]
Counts: Abstract 150 words; Maintext 2833 words; 29 References; 2 Figures, 2 Tables, Supplementary files 2 Tables and 1 Figure
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/mus.24175
Muscle & Nerve
Page 2 of 21 Running head: Recovery in CIM and CIP
ABSTRACT Introduction: Muscle weakness in critically ill patients after discharge varies. It is not known whether electrophysiological distinction between critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) during the early part of a patient’s stay in the intensive care unit (ICU) predicts long term prognosis. Methods: This was a prospective cohort study of mechanically ventilated ICU patients undergoing conventional nerve conduction studies and direct muscle stimulation in addition to neurological examination during their ICU stay and 1 year following ICU discharge. Results: 26 patients (7 ICU control, 8 CIM patients and 11 CIM/CIP patients) were evaluated 1 year after discharge from the ICU. 88% (n=7) of CIM patients recovered within 1 year, versus 55% (n=6) of CIM/CIP patients. 36% (n=4) of CIM/CIP patients still needed assistance during their daily routine (P=0.005). Discussion: Early electrophysiological testing predicts long term outcome in ICU survivors. CIM has a significant better prognosis than CIM/CIP.
Keywords: critical illness myopathy, critical illness polyneuropathy, direct muscle stimulation, intensive care unit, long term outcome
2 John Wiley & Sons, Inc.
Page 3 of 21
Muscle & Nerve Running head: Recovery in CIM and CIP
Introduction Muscle wasting and severe weakness are common clinical features of critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or a combination of both (CIM/CIP) [1-10]. Neuromuscular deficits may persist after discharge from the intensive care unit ( ICU), and may result in both physical limitations and poor health-related quality of life. Importantly, complete recovery within weeks has also been reported [10-19]. Follow-up studies in patients with ICU acquired weakness have not distinguished between CIM and CIP and have described outcomes ranging from complete recovery within weeks to persisting quadriplegia 5 years after discharge [11-14,17-19]. Two studies differentiated between CIM and CIP by routine nerve conduction studies and electromyography either at hospital discharge or admission to neuro-rehabilitation. Complete recovery within 3 to 6 months after ICU discharge was observed in all CIM patients, whereas 19% of CIP patients and 57% of CIM/CIP patients remained quadriplegic or quadriparetic for 1 to 5 years [15, 16]. The aim of this study was to determine whether early identification of, and distinction between, CIP and CIM permits prediction of long term neuromuscular outcome. This information may be useful in guiding interventions.
Materials and Methods Patients were recruited over an 18 month period upon admission to a 14-bed surgical ICU at the University Hospital. Inclusion criteria were defined as mechanical ventilation for more than 3 days and a Simplified Acute Physiology Score II (SAPS-II) of at least 20[20]. Patients with pre-existing myopathy, polyneuropathy, or cerebral or spinal injuries were excluded. Written informed consent of subjects or legal proxies was obtained during the ICU stay according to the ethical standards laid down in the 1964 Declaration of Helsinki and later amendments. The study was approved by the appropriate ethics committee.
3 John Wiley & Sons, Inc.
Muscle & Nerve
Page 4 of 21 Running head: Recovery in CIM and CIP
Patients underwent 2 examinations: The first took place within 2 weeks after ICU admission and included electrophysiological testing to classify patients as CIM, CIP, or CIM/CIP. A second examination including history, neurological examination, and electrophysiological testing was conducted 1 year after discharge from the ICU (mean 411 + 121 days). In order to monitor severity of illness during the ICU stay we assessed the SAPS-II . Development of organ failure during the ICU stay was assessed according to the sepsis related organ failure assessment[ 21] (SOFA) score. Richmond Agitation Sedation Scale (RASS) [22] scores were assessed daily in order to monitor immobility. Physical examination of muscle strength was conducted using the Medical Research Council (MRC) scale (range: 0 = no muscle contraction to 5 = normal strength)[23] at ICU discharge. Whenever possible, we examined 3 muscles in each limb. Assessment included triceps, biceps brachii, and extensor digitorum muscles in the upper limbs and rectus femoris, tibialis anterior, and gastrocnemius muscles in the lower limbs. MRC sum scores indicated overall muscle strength with MRC sum scores ranging from 0 to 60. Sum scores
Susanne Koch1, MD; Tobias Wollersheim1, Jeffrey Bierbrauer1, MD; Kurt Haas1, Rudolf Mörgeli1, Maria Deja1, PhD; Claudia D. Spies1, PhD; Simone Spuler2, PhD; Martin Krebs1, MD; Steffen Weber-Carstens1, PhD 1
Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and
Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany 2
Muscle Research Unit, Experimental and Clinical Research Center, Charité-
Universitätsmedizin Berlin, Lindenberger Weg 80, 13125 Berlin, Germany
Corresponding author: Susanne Koch, MD Dept. of Anesthesiology and Intensive Care Medicine Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Mitte Augustenburger Platz 1 D-13353 Berlin, Germany Tel: +49 30 450651808 FAX: +49 30 551909 e-mail: [email protected]
Counts: Abstract 150 words; Maintext 2833 words; 29 References; 2 Figures, 2 Tables, Supplementary files 2 Tables and 1 Figure
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/mus.24175
Muscle & Nerve
Page 2 of 21 Running head: Recovery in CIM and CIP
ABSTRACT Introduction: Muscle weakness in critically ill patients after discharge varies. It is not known whether electrophysiological distinction between critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) during the early part of a patient’s stay in the intensive care unit (ICU) predicts long term prognosis. Methods: This was a prospective cohort study of mechanically ventilated ICU patients undergoing conventional nerve conduction studies and direct muscle stimulation in addition to neurological examination during their ICU stay and 1 year following ICU discharge. Results: 26 patients (7 ICU control, 8 CIM patients and 11 CIM/CIP patients) were evaluated 1 year after discharge from the ICU. 88% (n=7) of CIM patients recovered within 1 year, versus 55% (n=6) of CIM/CIP patients. 36% (n=4) of CIM/CIP patients still needed assistance during their daily routine (P=0.005). Discussion: Early electrophysiological testing predicts long term outcome in ICU survivors. CIM has a significant better prognosis than CIM/CIP.
Keywords: critical illness myopathy, critical illness polyneuropathy, direct muscle stimulation, intensive care unit, long term outcome
2 John Wiley & Sons, Inc.
Page 3 of 21
Muscle & Nerve Running head: Recovery in CIM and CIP
Introduction Muscle wasting and severe weakness are common clinical features of critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or a combination of both (CIM/CIP) [1-10]. Neuromuscular deficits may persist after discharge from the intensive care unit ( ICU), and may result in both physical limitations and poor health-related quality of life. Importantly, complete recovery within weeks has also been reported [10-19]. Follow-up studies in patients with ICU acquired weakness have not distinguished between CIM and CIP and have described outcomes ranging from complete recovery within weeks to persisting quadriplegia 5 years after discharge [11-14,17-19]. Two studies differentiated between CIM and CIP by routine nerve conduction studies and electromyography either at hospital discharge or admission to neuro-rehabilitation. Complete recovery within 3 to 6 months after ICU discharge was observed in all CIM patients, whereas 19% of CIP patients and 57% of CIM/CIP patients remained quadriplegic or quadriparetic for 1 to 5 years [15, 16]. The aim of this study was to determine whether early identification of, and distinction between, CIP and CIM permits prediction of long term neuromuscular outcome. This information may be useful in guiding interventions.
Materials and Methods Patients were recruited over an 18 month period upon admission to a 14-bed surgical ICU at the University Hospital. Inclusion criteria were defined as mechanical ventilation for more than 3 days and a Simplified Acute Physiology Score II (SAPS-II) of at least 20[20]. Patients with pre-existing myopathy, polyneuropathy, or cerebral or spinal injuries were excluded. Written informed consent of subjects or legal proxies was obtained during the ICU stay according to the ethical standards laid down in the 1964 Declaration of Helsinki and later amendments. The study was approved by the appropriate ethics committee.
3 John Wiley & Sons, Inc.
Muscle & Nerve
Page 4 of 21 Running head: Recovery in CIM and CIP
Patients underwent 2 examinations: The first took place within 2 weeks after ICU admission and included electrophysiological testing to classify patients as CIM, CIP, or CIM/CIP. A second examination including history, neurological examination, and electrophysiological testing was conducted 1 year after discharge from the ICU (mean 411 + 121 days). In order to monitor severity of illness during the ICU stay we assessed the SAPS-II . Development of organ failure during the ICU stay was assessed according to the sepsis related organ failure assessment[ 21] (SOFA) score. Richmond Agitation Sedation Scale (RASS) [22] scores were assessed daily in order to monitor immobility. Physical examination of muscle strength was conducted using the Medical Research Council (MRC) scale (range: 0 = no muscle contraction to 5 = normal strength)[23] at ICU discharge. Whenever possible, we examined 3 muscles in each limb. Assessment included triceps, biceps brachii, and extensor digitorum muscles in the upper limbs and rectus femoris, tibialis anterior, and gastrocnemius muscles in the lower limbs. MRC sum scores indicated overall muscle strength with MRC sum scores ranging from 0 to 60. Sum scores
