Page last updated: 2024-10-31

neostigmine and Muscle Weakness

neostigmine has been researched along with Muscle Weakness in 27 studies

Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.
neostigmine : A quaternary ammonium ion comprising an anilinium ion core having three methyl substituents on the aniline nitrogen, and a 3-[(dimethylcarbamoyl)oxy] substituent at position 3. It is a parasympathomimetic which acts as a reversible acetylcholinesterase inhibitor.

Muscle Weakness: A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)

Research Excerpts

ExcerptRelevanceReference
" The aim of this clinical investigation was to assess the incidence of postoperative residual neuromuscular blockade in adult thoracic surgical patients administered neostigmine or sugammadex when optimal dosing and reversal strategies for these agents were used."5.41Neuromuscular and Clinical Recovery in Thoracic Surgical Patients Reversed With Neostigmine or Sugammadex. ( Avram, MJ; Benson, J; Bilimoria, S; Greenberg, SB; Maher, CE; Murphy, GS; Szokol, JW; Teister, KJ, 2021)
" Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase."3.79Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. ( Kotake, Y; Nakatsuka, I; Ochiai, R; Ogawa, S; Ozaki, M; Suzuki, T; Takagi, S; Takeda, J, 2013)
"Neostigmine was administered in adjusted doses after a train-of-four count of four was confirmed at the thumb."1.48Management of rocuronium neuromuscular block using a protocol for qualitative monitoring and reversal with neostigmine. ( Bhananker, SM; Cain, KC; Ng, IC; Thilen, SR; Treggiari, MM, 2018)
" Low dosage must be employed and repeated administration avoided."1.31Is vecuronium toxicity abolished by hemodialysis? A case report. ( Borsa, S; Pignataro, A; Pozzato, M; Quarello, F; Rollino, C; Vallero, A; Visetti, E, 2000)

Research

Studies (27)

TimeframeStudies, this research(%)All Research%
pre-199012 (44.44)18.7374
1990's1 (3.70)18.2507
2000's3 (11.11)29.6817
2010's10 (37.04)24.3611
2020's1 (3.70)2.80

Authors

AuthorsStudies
Murphy, GS2
Avram, MJ2
Greenberg, SB1
Bilimoria, S1
Benson, J1
Maher, CE1
Teister, KJ1
Szokol, JW2
Phillips, S2
Stewart, PA2
Thilen, SR1
Ng, IC1
Cain, KC1
Treggiari, MM1
Bhananker, SM1
Naguib, M2
Kopman, AF2
Kent, NB1
Liang, SS1
Smith, NA1
Khandkar, C1
Eikermann, M1
Kotake, Y2
Ochiai, R1
Suzuki, T2
Ogawa, S1
Takagi, S1
Ozaki, M2
Nakatsuka, I1
Takeda, J2
Brull, SJ1
Arkes, HR1
de Boer, HD1
Booij, LH1
Gupta, D1
BAUER, H1
SCHMID, O1
ROWLAND, LP1
KORENGOLD, MC1
JAFFE, IA1
BERG, L1
SHY, GM1
BARDIER, A1
MOULEDOUS, G1
REGNIER, C1
MARTINEZ, J1
PUJOL, M1
POLAK, W1
LAPRESLE, J1
BOUDIN, G1
GOULON, M1
HAMBURGER, J1
LHERMITTE, F1
PEQUIGNOT, H1
ADLER, E1
ERBSLOEH, F1
LALLEMAND, H1
THEVENARD, A1
Zank, LM1
Ng, J1
Neuman, GG1
SPATH, F1
BAYULKEM, F1
UNLUTURK, C1
OZBEK, A1
AVCILAR, HR1
RIDER, JA1
McDONALD, R1
Alkhazrajy, W1
Khorasanee, AD1
Russell, WJ1
Tramèr, MR1
Fuchs-Buder, T1
Rollino, C1
Visetti, E1
Borsa, S1
Pignataro, A1
Pozzato, M1
Vallero, A1
Quarello, F1

Clinical Trials (8)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Reversal of Neuromuscular Blockade in Thoracic Surgical Patients[NCT01837498]200 participants (Actual)Observational2014-02-28Completed
Incidence and Severity of Residual Neuromuscular Blockade With Application of a Protocol for Paralysis and Neostigmine Reversal of Rocuronium[NCT02660398]Phase 478 participants (Actual)Interventional2016-01-31Completed
Validation of the REPS Prediction Tool to Improve Quality of Perioperative Care[NCT03585400]101,510 participants (Actual)Observational2018-06-29Completed
Importance of Understanding Provider Variability in the Use of Neuromuscular Blocking Drugs and Reversal Agents[NCT03585348]265,537 participants (Actual)Observational2018-06-29Completed
Development of an Algorithm Using Clinical Tests to Avoid Post-operative Residual Neuromuscular Block[NCT03219138]265 participants (Actual)Interventional2008-01-08Completed
Optimal Dose of Combination of Rocuronium and Cisatracurium: A Randomized Double-blinded Clinical Trial[NCT02495038]81 participants (Actual)Interventional2014-03-31Completed
A Randomized, Blinded-assessor, Single Center Study to Determine if Administration of Sugammadex, When Used to Reverse Deep Neuromuscular Blockade (NMB) After Open Abdominal Surgery, Impacts Hospital Efficiency[NCT02860507]Phase 450 participants (Actual)Interventional2016-08-31Completed
A Prospective Evaluation of an Anesthesia Protocol to Reduce Post-operative and Post-discharge Nausea and Vomiting in a High Risk Orthognathic Surgery Population[NCT01592708]233 participants (Actual)Interventional2012-06-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Additional Rescue Doses Per Hour Ratio.

Additional Rescue Doses Per Hour Ratio is the number per hour of addition of rescue dose administrated with 10% of initial NMBAs dose. The formula is {(Addition number + 1 / Anesthetic time) x 60}. (NCT02495038)
Timeframe: Intraoperative, an average of 3 hours.

Interventionratio (Mean)
Intubating Dose, Group I1.43455
10% Reduction of Combination of Esmeron® and Nimbex®, Group S1.21014
20% Reduction of Combination of Esmeron® and Nimbex®, Group L0.82128

Anesthetic Time

Time from induction to recovery of anesthesia, asessed up to 3 hours. (NCT02495038)
Timeframe: Intraoperative, an average 4 hours.

InterventionMinute (Mean)
Intubating Dose, Group I163.0
10% Reduction of Combination of Esmeron® and Nimbex®, Group S159.9
20% Reduction of Combination of Esmeron® and Nimbex®, Group L161.4

Bispectral Index

"The BIS monitor provides a single dimensionless number, which ranges from 0 (equivalent to EEG silence) to 100. A BIS value between 40 and 60 indicates an appropriate level for general anesthesia, as recommended by the manufacturer.~Before induction of anesthesia, bispectral index was measured for baseline. And after injection of NMBAs, bispectral index was measured at 10 min." (NCT02495038)
Timeframe: Before and after induction of anesthesia, an average 10 min.

InterventionBIS score (Mean)
Intubating Dose, Group I46.0
10% Reduction of Combination of Esmeron® and Nimbex®, Group S46.1
20% Reduction of Combination of Esmeron® and Nimbex®, Group L44.3

Body Temperature

"Before induction of anesthesia, body temperature was measured for baseline by oral temperature probe.~And after injection of NMBAs, non invasive blood pressure was measured at 10 min by esophageal temperature probe." (NCT02495038)
Timeframe: Before and after induction of anesthesia, an average 10 min.

InterventionCelcius degree (Mean)
Intubating Dose, Group I36.3
10% Reduction of Combination of Esmeron® and Nimbex®, Group S36.3
20% Reduction of Combination of Esmeron® and Nimbex®, Group L36.3

Duration 25% of Neuromuscular Blocking Agents(NMBAs)

Time from administration of initial NMBAs to Train-of-four (TOF) ratio >25%, assessed up to 2 hours during general anesthesia. (NCT02495038)
Timeframe: Intraoperative, an average of 1 hours

InterventionMinute (Mean)
Intubating Dose, Group I51.3
10% Reduction of Combination of Esmeron® and Nimbex®, Group S47.9
20% Reduction of Combination of Esmeron® and Nimbex®, Group L39.4

Onset of Neuromuscular Blocking Agents(NMBAs)

Time from administration of initial NMBAs to Train-of-four (TOF) ratio=0, assessed up to 15 minutes during general anesthesia. (NCT02495038)
Timeframe: Intraoperative, an average of 5 minutes

InterventionSecond (Mean)
Intubating Dose, Group I212.8
10% Reduction of Combination of Esmeron® and Nimbex®, Group S230.1
20% Reduction of Combination of Esmeron® and Nimbex®, Group L399.3

Operation Time

Time from skin incision to wound dressing assessed up to 8 hours. (NCT02495038)
Timeframe: Intraoperative, an average of 3 hours.

InterventionMinute (Mean)
Intubating Dose, Group I151.8
10% Reduction of Combination of Esmeron® and Nimbex®, Group S147.0
20% Reduction of Combination of Esmeron® and Nimbex®, Group L145.9

Peripheral Oxygen Saturation

"Before induction of anesthesia, peripheral oxygen saturation was measured for baseline.~And after injection of NMBAs, peripheral oxygen saturation was measured at 10 min." (NCT02495038)
Timeframe: Before and after induction of anesthesia, an average 10 min.

InterventionPercentage (Mean)
Intubating Dose, Group I100
10% Reduction of Combination of Esmeron® and Nimbex®, Group S99.9
20% Reduction of Combination of Esmeron® and Nimbex®, Group L100

Recovery Index of Neuromuscular Blocking Agents(NMBAs)

Time from TOF ratio 25% to 75%, assessed up to 1 hour during general anesthesia. (NCT02495038)
Timeframe: Intraoperative, an average of 20 minutes

InterventionMinute (Mean)
Intubating Dose, Group I15.9
10% Reduction of Combination of Esmeron® and Nimbex®, Group S16.2
20% Reduction of Combination of Esmeron® and Nimbex®, Group L14.1

Non Invasive Blood Pressure,

"Before induction of anesthesia, non invasive blood pressure was measured for baseline.~And after injection of NMBAs, non invasive blood pressure was measured at 10 min." (NCT02495038)
Timeframe: Before and after induction of anesthesia, an average 10 min.

,,
InterventionmmHg (Mean)
Systolic pressureDiastolic pressure
10% Reduction of Combination of Esmeron® and Nimbex®, Group S128.376.7
20% Reduction of Combination of Esmeron® and Nimbex®, Group L128.474.8
Intubating Dose, Group I128.375.6

Number of Patients Who Experience Postoperative Nausea and Vomiting, Post-operative Pain, and Post-operative Complications

(NCT02860507)
Timeframe: through discharge from hospital, average of 72 hours

InterventionParticipants (Count of Participants)
Neostigmine + Glycopyrrolate8
Sugammadex10

Operating Room (OR) Turnover Time When Using Sugammadex Instead of Combination of Neostigmine and Glycopyrrolate.

(NCT02860507)
Timeframe: through start of next surgery, average of 2 hours

InterventionMinutes (Mean)
Neostigmine + Glycopyrrolate49.7
Sugammadex49.45

Hospital Length of Stay

Anesthesia start time determined from anesthesia portion of the medical record. Time at which discharge order was placed will serve as time of discharge. (NCT01592708)
Timeframe: Anesthesia start time to placement of hospital discharge order - average 26 - 28 hours

Interventionhours (Median)
Intervention Cohort26.4
Comparison Cohort28.2

Post-discharge Nausea

To be assessed based on patient diary completed daily for 1 week following discharge to home from the hospital (NCT01592708)
Timeframe: 1 week from discharge from hospital

Interventionpercentage of subjects with PDN (Number)
Intervention Cohort72
Comparison Cohort60

Post-discharge Vomiting

(NCT01592708)
Timeframe: 1 week post discharge

Interventionpercentage of subjects with PDV (Number)
Intervention Cohort22
Comparison Cohort29

Post-operative Nausea

End of surgery time determined by anesthesia portion of the medical record. PONV to be assessed by review of surgeons' and nurses' notes in the medical record as well as through review of patient diaries. Vomiting constitutes a safety issue and, as such, associated adverse events will be noted. (NCT01592708)
Timeframe: End of surgery to discharge from hospital

Interventionpercentage of subjects with PON (Number)
Intervention Cohort24
Comparison Cohort70

Post-operative Vomiting

(NCT01592708)
Timeframe: End of surgery to discharge from hospital

Interventionpercentage of subjects with POV (Number)
Intervention Cohort11
Comparison Cohort28

Reviews

1 review available for neostigmine and Muscle Weakness

ArticleYear
Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review.
    British journal of anaesthesia, 1999, Volume: 82, Issue:3

    Topics: Cholinesterase Inhibitors; Humans; Muscle Weakness; Neostigmine; Neuromuscular Blocking Agents; Post

1999
Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review.
    British journal of anaesthesia, 1999, Volume: 82, Issue:3

    Topics: Cholinesterase Inhibitors; Humans; Muscle Weakness; Neostigmine; Neuromuscular Blocking Agents; Post

1999
Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review.
    British journal of anaesthesia, 1999, Volume: 82, Issue:3

    Topics: Cholinesterase Inhibitors; Humans; Muscle Weakness; Neostigmine; Neuromuscular Blocking Agents; Post

1999
Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review.
    British journal of anaesthesia, 1999, Volume: 82, Issue:3

    Topics: Cholinesterase Inhibitors; Humans; Muscle Weakness; Neostigmine; Neuromuscular Blocking Agents; Post

1999

Trials

3 trials available for neostigmine and Muscle Weakness

ArticleYear
Neuromuscular and Clinical Recovery in Thoracic Surgical Patients Reversed With Neostigmine or Sugammadex.
    Anesthesia and analgesia, 2021, 08-01, Volume: 133, Issue:2

    Topics: Aged; Aged, 80 and over; Anesthesia Recovery Period; Delayed Emergence from Anesthesia; Female; Huma

2021
Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer study.
    Anaesthesia, 2018, Volume: 73, Issue:9

    Topics: Adult; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Admini

2018
Antagonism of cisatracurium and rocuronium block at a tactile train-of-four count of 2: should quantitative assessment of neuromuscular function be mandatory?
    Anesthesia and analgesia, 2004, Volume: 98, Issue:1

    Topics: Adolescent; Adult; Aged; Androstanols; Anesthesia Recovery Period; Atracurium; Cholinesterase Inhibi

2004

Other Studies

23 other studies available for neostigmine and Muscle Weakness

ArticleYear
Catching a Unicorn: Neostigmine and Muscle Weakness-Not Neostigmine for All, but Quantitative Monitoring for Everyone!
    Anesthesiology, 2018, Volume: 129, Issue:2

    Topics: Conditioning, Psychological; Humans; Muscle Weakness; Neostigmine

2018
In Reply.
    Anesthesiology, 2018, Volume: 129, Issue:2

    Topics: Humans; Muscle Weakness; Neostigmine

2018
Management of rocuronium neuromuscular block using a protocol for qualitative monitoring and reversal with neostigmine.
    British journal of anaesthesia, 2018, Volume: 121, Issue:2

    Topics: Adult; Aged; Airway Extubation; Clinical Protocols; Cohort Studies; Female; Humans; Incidence; Male;

2018
Neostigmine-induced weakness: what are the facts?
    Anaesthesia, 2018, Volume: 73, Issue:9

    Topics: Double-Blind Method; Humans; Muscle Weakness; Neostigmine; Neuromuscular Blockade; Neuromuscular Non

2018
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Adult; Aged; Airway Extubation; Androstanols; Anesthesia Recovery Period; Chi-Square Distribution; C

2013
Reasoning of an anomaly: residual block after sugammadex.
    Anesthesia and analgesia, 2013, Volume: 117, Issue:2

    Topics: Androstanols; Cholinesterase Inhibitors; Female; gamma-Cyclodextrins; Humans; Male; Muscle Weakness;

2013
Why are we using pulse oximetry but not neuromuscular monitoring routinely: the real world scenario?
    Anesthesia and analgesia, 2014, Volume: 118, Issue:3

    Topics: Androstanols; Cholinesterase Inhibitors; Female; gamma-Cyclodextrins; Humans; Male; Muscle Weakness;

2014
In response.
    Anesthesia and analgesia, 2014, Volume: 118, Issue:3

    Topics: Androstanols; Cholinesterase Inhibitors; Female; gamma-Cyclodextrins; Humans; Male; Muscle Weakness;

2014
RESIDUAL NEUROMUSCULAR BLOCKADE (RNMB): ROCURONIUM'S DEFASCICULATING DOSE, NEOSTIGMINE- INDUCED WEAKNESS, AND AWARENESS DURING RECOVERY.
    Middle East journal of anaesthesiology, 2015, Volume: 23, Issue:2

    Topics: Androstanols; Anesthesia Recovery Period; Awareness; Electromyography; Humans; Muscle Weakness; Neos

2015
[A case of Erb-Goldflam myasthenia. Trial of a new anti-myasthenic product].
    Revue d'oto-neuro-ophtalmologie, 1953, Volume: 25, Issue:3

    Topics: Humans; Muscle Weakness; Myasthenia Gravis; Neostigmine

1953
[Chemotherapy of myasthenia].
    Deutsche Zeitschrift fur Nervenheilkunde, 1953, Volume: 169, Issue:6

    Topics: Muscle Weakness; Myasthenia Gravis; Neostigmine

1953
Prostigmine-induced muscle weakness in myasthenia gravis patients.
    Neurology, 1955, Volume: 5, Issue:2

    Topics: Humans; Muscle Weakness; Muscles; Myasthenia Gravis; Neostigmine; Paresis

1955
[ERB-GOLDFLAM MYASTHENIA IN A 4-YEAR-OLD CHILD].
    Archives francaises de pediatrie, 1964, Volume: 21

    Topics: Child; Deglutition Disorders; Electromyography; Eyelids; Humans; Muscle Weakness; Myasthenia Gravis;

1964
[A CASE OF PSEUDOPARALYTIC MYESTHENIA GRAVIS IN AN INFANT].
    Archivos de pediatria del Uruguay, 1964, Volume: 35

    Topics: Electromyography; Eyelids; Humans; Infant; Muscle Weakness; Myasthenia Gravis; Neostigmine

1964
[HOW TO TREAT MYASTHENIA].
    La Presse medicale, 1964, Oct-10, Volume: 72

    Topics: Ambenonium Chloride; Ephedrine; Humans; Muscle Weakness; Myasthenia Gravis; Neostigmine; Physostigmi

1964
[THE THYMUS-MYASTHENIA PROBLEM FROM THE VIEWPOINT OF THE SURGEON].
    Munchener medizinische Wochenschrift (1950), 1965, May-14, Volume: 107

    Topics: Drug Therapy; Humans; Muscle Weakness; Myasthenia Gravis; Neostigmine; Surgeons; Thymectomy; Thymoma

1965
[THYMECTOMY IN THE TREATMENT OF SEVERE MYASTHENIA].
    Deutsche medizinische Wochenschrift (1946), 1965, Apr-30, Volume: 90

    Topics: Acidosis; Acidosis, Respiratory; Bulbar Palsy, Progressive; Drug Therapy; Muscle Weakness; Myastheni

1965
[The quick clinical diagnosis of myasthenia in its beginning; value of the orbicular sign of the eyelids and this finding combined with the prostigmine injection test].
    La Presse medicale, 1955, Jan-08, Volume: 63, Issue:2

    Topics: Eyelids; Humans; Muscle Weakness; Myasthenia Gravis; Neostigmine; Physical Examination

1955
[Myasthenia and the thymus].
    Langenbecks Archiv fur klinische Chirurgie ... vereinigt mit Deutsche Zeitschrift fur Chirurgie, 1951, Volume: 267

    Topics: Muscle Weakness; Myasthenia Gravis; Neostigmine; Thymus Gland

1951
[Case of Erb-Goldflam disease (myasthenia)].
    Turk Tip Cemiyeti mecmuasi, 1951, Volume: 17, Issue:10

    Topics: Humans; Muscle Weakness; Myasthenia Gravis; Neostigmine

1951
Myasthenia gravis in a case of malignant thymoma resistant to neostigmine therapy.
    The American journal of the medical sciences, 1950, Volume: 219, Issue:1

    Topics: Humans; Muscle Weakness; Myasthenia Gravis; Neoplasms; Neostigmine; Thymoma; Thymus Gland

1950
Muscle weakness after muscle relaxants: an audit of clinical practice.
    Anaesthesia and intensive care, 2004, Volume: 32, Issue:2

    Topics: Age Factors; Androstanols; Anesthesia, General; Cholinesterase Inhibitors; Female; Hand Strength; Hu

2004
Is vecuronium toxicity abolished by hemodialysis? A case report.
    Artificial organs, 2000, Volume: 24, Issue:5

    Topics: Cholinesterase Inhibitors; Female; Graft Rejection; Humans; Kidney Transplantation; Middle Aged; Mus

2000