Malignant Hyperthermia Testing in Probands with No Adverse … · 2018. 4. 2. · Malignant...
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Malignant Hyperthermia Testing in Probands with No Adverse Anesthetic Reaction Table-3 Dantrolene in MHS patients Responsive Non responsive P value Dantrolene given (n=40) 30 (75.0%) 10 (25.0%) P< 0.001 Pre treatment CK (IU/L), mean (SD) median (range) 512.5 (735.1) 320 (32 – 3381) 319.9 (475.0) 120 (45-1500) 0.16 Post-Exercise Rhabdo and/ or Exercise Intolerance 2 (6.5%) 0 (0%) 0.55 Post-viral chronic fatigue 15(50.0%) 4(40.0%) 0.24 Conclusion University of Toronto MH susceptibility, as confirmed by CHCT, may predispose patients to a variety of non-anesthetic induced muscle abnormalities. Our results support the contention that MH maybe more than an anesthetic-related disorder but should be interpreted in the context of the limitations of the sensitivity of the CHCT. Results Table-1 Compiled Reasons for Referred Probands MHS (n=104) MHN (n=48) Baseline high CK (CK>250 IU/L) 59 (56.7%) 18 (37.5%) Post Exercise Rhabdomylosis and /or Exercise Intolerance a 10 (9.6%) 2 (4.1%) Post viral chronic fatigue 36 (34.6%) 27 (56.2%) Heat Stroke 0 (0%) 1 (2%) a One patient was referred for both high CK and post-exercise rhabdomyolysis (listed in both). • Between 1992-2012, out of 525 referred probands, 152 were identified with no anesthetic reaction (Table 1). • From these, 104 (68.4%) probands had positive CHCT. • Reasons for referrals, shown in Table 1, included unexplained high creatine kinase (CK), post-viral fatigue, post-exercise rhabdomyolysis, and heat stroke. • Mean CK levels were significantly higher in the group with positive CHCT (687.5 vs. 321.3, p=0.013) (Table 2). • Thirty-eight (36.5%) patients, all with positive CHCT, had abnormal histomorphology, including central cores and multi- minicores. • Three patients with positive CHCT carried causative RYR1 mutations. They were referred for unexplained high CK or exercise-induced rhabdomyolysis. • Forty patients with positive CHCT (38.4%) received oral dantrolene, 30 of whom (75.0%) responded with improvement of symptoms and reduction in CK (Table 3). Table-2 Characteristics of the Referred Probands MHS (n=104) MHN (n=48) P Value Demographics Age (year), mean (SD) median (range) 37.0 (11.8) 35 (28-62) 40.5 (17.1) 39 (25-58) 0.40 Male sex 87(83.6%) 42(87.05) 0.36 Caucasian 100(96.2%) 48(100%) 0.21 Symptoms Cramps 10 (11.3%) 10 (17.4%) Muscle pain 4 (1.9%) 4 (0%) Weakness 1 (2.8%) 2(0%) Heat intolerance 2 (1.9%) 2 (4.3%) 2 of above symptoms 35 (34.9%) 11 (19.6%) 3 of above symptoms 32 (32.0%) 18 (34.8%) No symptoms 14(13.5%) 13 (27.0%) 0.37 Unremarkable anesthetics 28(26.9%) 12(25.0%) CK (IU/L), mean (SD) median (range) 687.5 (905.8) 669.5 (23-7000) 321.3(370.52) 518 (23-1210) 0.013 Genetic testing- RYR1 mutations 3/47 (6.4%) 0/3 (0%) 1.00 Abnormal Histomorphology 38 (36.5%) 0 (0%) P<0.0001 Background Following institutional research ethics board approval, all CHCT- tested probands at our center were identified. •Patients with anesthetic reactions were excluded. •Data was collected on reasons for referrals, baseline CK, musculoskeletal symptoms, genetics results, and histopathology. •The fatigue was defined as muscle pain, weakness and cramps, interfering with functional ability and lasted more than 3 months after the onset of viral illness. •Positive CHCT was defined based on the standardized North American CHCT test protocol. •Data was analyzed and compared between patients with positive and negative CHCT results. •Response to dantrolene among patients with positive CHCT was assessed. •Wilcoxon rank sums test, and Fisher’s exact test were used for numerical and categorical parameters, respectively. Funded by the Department of Anesthesia, University of Toronto Merit award (Toronto, Ontario, Canada) to Sheila Riazi. Malignant hyperthermia (MH) is characterized by a potentially fatal adverse reaction to volatile anesthetic, and /or succinylcholine. Typically, patients will undergo caffeine-halothane contracture (CHCT) and / or genetic testing following an adverse anesthetic reaction or positive family history. However, sometimes patients with no individual or family history of anesthetic reaction are referred for MH testing due to a variety of reasons, such as idiopathic increased in creatine kinase (CK) values, or heat/exercise rhabdomyolysis. The objective of our study was to investigate reasons for referrals in these non-anesthetic cases and to assess their phenotypes. Methods
Transcript of Malignant Hyperthermia Testing in Probands with No Adverse … · 2018. 4. 2. · Malignant...
Malignant Hyperthermia Testing in Probands with No Adverse Anesthetic Reaction
Table-3 Dantrolene in MHS patients Responsive Non responsive P value Dantrolene given (n=40) 30 (75.0%) 10 (25.0%) P< 0.001
Pre treatment CK (IU/L), mean (SD) median (range)
512.5 (735.1) 320 (32 –
3381)
319.9 (475.0) 120 (45-1500)
0.16
Post-Exercise Rhabdo and/ or Exercise Intolerance
2 (6.5%) 0 (0%) 0.55
Post-viral chronic fatigue 15(50.0%) 4(40.0%) 0.24
Conclusion
University of Toronto
MH susceptibility, as confirmed by CHCT, may predispose patients to a variety of non-anesthetic induced muscle abnormalities. Our results support the contention that MH maybe more than an anesthetic-related disorder but should be interpreted in the context of the limitations of the sensitivity of the CHCT.
Results
Table-1 Compiled Reasons for Referred Probands MHS (n=104) MHN (n=48) Baseline high CK (CK>250 IU/L) 59 (56.7%) 18 (37.5%) Post Exercise Rhabdomylosis and /or Exercise Intolerancea
10 (9.6%) 2 (4.1%)
Post viral chronic fatigue 36 (34.6%) 27 (56.2%) Heat Stroke 0 (0%) 1 (2%) a One patient was referred for both high CK and post-exercise rhabdomyolysis (listed in both).
• Between 1992-2012, out of 525 referred probands, 152 were identified with no anesthetic reaction (Table 1).
• From these, 104 (68.4%) probands had positive CHCT. • Reasons for referrals, shown in Table 1, included unexplained
high creatine kinase (CK), post-viral fatigue, post-exercise rhabdomyolysis, and heat stroke.
• Mean CK levels were significantly higher in the group with positive CHCT (687.5 vs. 321.3, p=0.013) (Table 2).
• Thirty-eight (36.5%) patients, all with positive CHCT, had abnormal histomorphology, including central cores and multi-minicores.
• Three patients with positive CHCT carried causative RYR1 mutations. They were referred for unexplained high CK or exercise-induced rhabdomyolysis.
• Forty patients with positive CHCT (38.4%) received oral dantrolene, 30 of whom (75.0%) responded with improvement of symptoms and reduction in CK (Table 3).
Table-2 Characteristics of the Referred Probands MHS (n=104) MHN (n=48) P Value Demographics Age (year), mean (SD) median (range)
37.0 (11.8) 35 (28-62)
40.5 (17.1) 39 (25-58)
0.40
Male sex 87(83.6%) 42(87.05) 0.36 Caucasian 100(96.2%) 48(100%) 0.21 Symptoms
Cramps 10 (11.3%) 10 (17.4%) Muscle pain 4 (1.9%) 4 (0%) Weakness 1 (2.8%) 2(0%) Heat intolerance 2 (1.9%) 2 (4.3%) 2 of above symptoms 35 (34.9%) 11 (19.6%) 3 of above symptoms 32 (32.0%) 18 (34.8%) No symptoms 14(13.5%) 13 (27.0%) 0.37 Unremarkable anesthetics
28(26.9%)
12(25.0%)
CK (IU/L), mean (SD) median (range)
687.5 (905.8) 669.5 (23-7000)
321.3(370.52) 518 (23-1210)
0.013
Genetic testing- RYR1 mutations
3/47 (6.4%)
0/3 (0%)
1.00
Abnormal Histomorphology 38 (36.5%) 0 (0%) P<0.0001
Background
Following institutional research ethics board approval, all CHCT-tested probands at our center were identified. •Patients with anesthetic reactions were excluded. •Data was collected on reasons for referrals, baseline CK, musculoskeletal symptoms, genetics results, and histopathology. •The fatigue was defined as muscle pain, weakness and cramps, interfering with functional ability and lasted more than 3 months after the onset of viral illness. •Positive CHCT was defined based on the standardized North American CHCT test protocol. •Data was analyzed and compared between patients with positive and negative CHCT results. •Response to dantrolene among patients with positive CHCT was assessed. •Wilcoxon rank sums test, and Fisher’s exact test were used for numerical and categorical parameters, respectively.
Funded by the Department of Anesthesia, University of Toronto Merit award (Toronto, Ontario, Canada) to Sheila Riazi.
Malignant hyperthermia (MH) is characterized by a potentially fatal adverse reaction to volatile anesthetic, and /or succinylcholine. Typically, patients will undergo caffeine-halothane contracture (CHCT) and / or genetic testing following an adverse anesthetic reaction or positive family history. However, sometimes patients with no individual or family history of anesthetic reaction are referred for MH testing due to a variety of reasons, such as idiopathic increased in creatine kinase (CK) values, or heat/exercise rhabdomyolysis. The objective of our study was to investigate reasons for referrals in these non-anesthetic cases and to assess their phenotypes.
Methods
