Society for Pediatric Anesthesia Section Editor: Peter J. Davis
Malignant Hyperthermia in Children: An Analysis of the North American Malignant Hyperthermia Registry Priscilla Nelson, MD, and Ronald S. Litman, DO BACKGROUND: Clinical characteristics of malignant hyperthermia (MH) in pediatric patients have not been elucidated. In this study, we used the North American Malignant Hyperthermia Registry to determine differences in clinical characteristics of acute MH across pediatric age groups. We hypothesized that there are differences in clinical presentation, clinical course, and outcomes, which correlate with age. A secondary aim was to determine the types of preexisting medical conditions associated with pediatric MH. METHODS: We performed a retrospective review of the North American Malignant Hyperthermia Registry to identify pediatric subjects (up to and including 18 years) with an MH clinical grading score at or above 35 indicating “very likely” or “almost certain” MH. Preoperative patient characteristics, perianesthetic factors, and outcome data were compared for 3 cohorts based on age: 0 to 24 months, 25 months to 12 years, and 13 to 18 years. We used statistical analysis to determine differences among the groups. RESULTS: We analyzed 264 records: 35 in the youngest age group, 163 in the middle age group, and 66 in the oldest group. There was no indication of any predisposing risk factors for MH based on family history or physical examination. Sinus tachycardia, hypercarbia, and rapid temperature increase were the most common signs of acute MH (observed in 73.1%, 68.6%, and 48.5%, respectively) and were more common in the oldest age cohort. Higher maximum temperatures and higher peak potassium values were seen in the oldest age cohort. Masseter spasm was more common in the middle age cohort. The youngest age cohort was more likely to develop skin mottling and was approximately half as likely to develop muscle rigidity. The youngest age group also demonstrated significantly higher peak lactic acid levels and lower peak creatine kinase values. Treatments were similar across age cohorts. There were 10 MH-associated deaths, 6 in the middle age group and 4 in the oldest age group. Recrudescence of symptoms after initial treatment occurred in 14.4% of subjects, with no difference across age cohorts. Two of these subjects, 1 in the middle age group and 1 in the oldest age group, died after the recrudescence event. CONCLUSIONS: There are differences in clinical characteristics of acute MH among different age cohorts in childhood. Older subjects demonstrated higher body temperatures and higher potassium levels, and the youngest subjects had greater levels of metabolic acidosis. Most children in each age group were phenotypically normal before developing MH. (Anesth Analg 2014;118:369–74)
A
pproximately 17% of cases of malignant hyperthermia (MH) occur in children,1 yet the clinical characteristics of MH in the pediatric population have not been fully elucidated. Gaps in knowledge include preoperative risk stratification as well as clinical presentations and responses to treatment that are unique to children based on developmental age.
From the Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Accepted for publication August 7, 2013. Funding: Departmental sources only: Children’s Anesthesia Associates. The authors declare no conflicts of interest. This report was previously presented, in part, at the Annual meeting of the American Society of Anesthesiologists, Washington, DC, October 2012. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.anesthesia-analgesia.org). Reprints will not be available from the authors. Address correspondence to Ronald S. Litman, DO, Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, 34th St., Civic Center Blvd, Philadelphia, PA 19104. Address e-mail to [email protected]. Copyright © 2013 International Anesthesia Research Society DOI: 10.1213/ANE.0b013e3182a8fad0
February 2014 • Volume 118 • Number 2
The primary aim of this study was to use data from the North American Malignant Hyperthermia Registry (NAMHR)2,3 to determine the differences in clinical characteristics of acute MH across pediatric age populations. Given the developmental changes in body structure and composition throughout childhood, we hypothesized that there are differences in clinical presentation, clinical course, and outcomes based on the age group of the patient. A secondary aim was to determine the types of preexisting medical conditions that were associated with pediatric MH cases.
METHODS
We obtained permission from the IRB of the Stokes Research Institute of The Children’s Hospital of Philadelphia (requirement for written consent was waived by the IRB because the database was de-identified at its source) to conduct a retrospective analysis of all subjects up to and including 18 years of age in the NAMHR with an MH clinical grading scale (CGS) score at or above 35, indicating “very likely” or “almost certain” MH. The CGS represents a qualitative score of the likelihood that an MH event occurred, on the basis of clinical characteristics and laboratory results.4 www.anesthesia-analgesia.org
369
Malignant Hyperthermia in Children
The NAMHR database is divided into 3 general categories of data that correspond to the data fields of the Adverse Metabolic or Muscular Reaction to Anesthesia (AMRA) Report (Appendix, see Supplemental Digital Content 1, http://links.lww.com/AA/A601): (1) preoperative patient demographics and risk factors; (2) clinical characteristics of the acute MH event; and (3) postevent clinical characteristics and outcomes. The database was supplied to us in an Excel spreadsheet format (Microsoft, Redwood, WA).
Statistical Analyses
To test our hypotheses, we divided eligible subjects into 3 agebased cohorts: 0 to 24 months (youngest age group), 25 months to 12 years (middle age group), and 13 to 18 years (oldest age group). Comparisons of variables of interest among age cohorts were performed with Stata IC 10.1 (College Station, TX), using the Kruskal-Wallis test to analyze continuous variables and χ2 or Fisher exact test to compare categorical variables. Statistical significance was defined as P < 0.05.
RESULTS
There were 351 subjects aged 18 years and younger in the NAMHR, stemming from events that occurred between 1960 and 2011. When these records were subjected to a screen based on the MH CGS score, we obtained 264 (75.2%) records that met the criteria for MH as “very likely” or “almost certain.” Of these, 35 belonged to the youngest age group, 163 in the middle age group, and 66 in the oldest age group.
Preoperative Patient Demographics and Risk Factors
Most subjects in our cohort were male; although this predominance held across age cohorts, it was more pronounced in the oldest age group (P = 0.04) (Table 1). Most subjects were Caucasian; no significant differences were noted in racial composition among age groups. Although the youngest cohort trended towards a higher family history of MH (P = 0.09), there appeared to be no differences between the age groups with regard to family history of MH-related events or illnesses. Forty-nine subjects (18.5%) had a family history of MH or other MH-related illness, but this did not significantly differ by age group. The youngest age group trended toward being more likely to have generalized muscle weakness (P = 0.07) and was noted to have a higher incidence of undescended testes (P = 0.04) and inguinal hernia (P = 0.04). These differences are likely related to a surgical case-based bias. No difference was noted in the number of prior anesthetic procedures, but the MH event was the first procedure for 50% of patients and the second procedure for 20% (not shown in Table 1). The case type by service was distributed across specialties, with cases most commonly involving ear, nose, and throat (29%) and orthopedics (21.2%). The type of case was variable by age group, with urological cases accounting for nearly 30% of the youngest group events (P ≤ 0.001), earnose-throat cases accounting for nearly 40% of the middle group events (P ≤ 0.001), and orthopedic cases accounting for 50% of oldest cohort events (P ≤ 0.001). Cases for the youngest group were nearly all scheduled, while the adolescent cohort had a higher percentage of emergent procedures
370 www.anesthesia-analgesia.org
(P ≤ 0.001). Although denominators for non-MH cases are not available, these case distributions are likely reflective of a typical case distribution in children by age group. Most children had induction of general anesthesia with IV drugs, although the youngest group was more likely to receive an inhaled induction (P = 0.003). As expected, IV induction was significantly associated with emergent cases (97.4% vs 80.9%, P = 0.009). The youngest age group was less likely to receive IV succinylcholine (P ≤ 0.001), vecuronium (P = 0.001), propofol (P ≤ 0.001), or fentanyl (P < 0.001) but was more likely to receive halothane (P < 0.001) or sevoflurane (P = 0.013) compared with the older cohorts. These results are also likely explained by normal age-based clinical practice.
Event Characteristics
Sinus tachycardia, hypercarbia, and rapid temperature increase were the most commonly observed physical examination findings (observed in 73.1%, 68.6%, and 48.5%, respectively) (Table 2); the oldest cohort was more likely to develop these findings. The oldest age group took longer to reach their maximum end-tidal CO2 value, had higher peak potassium values, and was more likely to demonstrate sweating during the event. The middle age cohort had a lower maximum end-tidal CO2 and blood gas Pco2 compared with the youngest and oldest age groups. The middle age cohort was more likely to develop masseter spasm, and the youngest age cohort was more likely to develop skin mottling. Although no significant differences were noted in the incidence of generalized muscle rigidity, dark colored urine, tachypnea, cyanosis, ventricular arrhythmias, or overall temperature increase among age groups, the youngest age cohort was approximately half as likely to demonstrate muscle rigidity. Masseter spasm was significantly more common in children who received succinylcholine (75/125 vs 11/128, P < 0.001). However, there were differences when analyzed separately by age group. For example, although infrequently used in subjects in the youngest age group, masseter spasm and subsequent MH occurred in 4 of the 5 subjects in this age group who received succinylcholine. In the oldest age group, there was no significant difference in appearance of masseter spasm between the subjects who did and did not receive succinylcholine (P = 0.17). Subjects in the oldest age cohort reached a higher maximum temperature compared with those in the youngest and middle cohorts; subjects in the youngest age group tended to take longer to reach their maximum value (P = 0.07), and they tended to have a lower blood pH (P = 0.06). Subjects in the youngest age group also demonstrated significantly higher peak lactic acid levels (P = 0.0025) and lower peak creatine kinase (P ≤ 0.001) values.
Treatments and Outcomes
For nearly all treatments, regimens were similar across age cohorts. The oldest age cohort was more likely to receive active cooling (they had higher temperatures) and fluid administration (Table 3). The older cohort more commonly received glucose and insulin in their treatment, which likely related to their higher potassium values. Dantrolene was administered in >73% of events, with the average initial and
anesthesia & analgesia
Table 1. Patient Demographics and Procedural Characteristics Youngest (n = 35) Characteristic Male Female Race Caucasian Hispanic African American Native American Hawaiian/Pacific islander African East Asian South Asian Middle Eastern Other race not listed Family history Malignant hyperthermia Masseter rigidity Intraoperative event Sudden infant death syndrome Sudden death Heat stroke Heat intolerance Myopathy Any family history (from the above) Physical exam findings Increased muscle tone Decreased muscle tone General muscle weakness Myopathy Ptosis Strabismus Hiatal hernia Inguinal hernia Umbilical hernia Undescended testicles Clubbed foot Joint hypermobility Kyphoscoliosis Winged scapulae Skeletal fractures Case type Cardiothoracic Dental Ear, nose, and throat Ophthalmology General surgery Gynecology Neurosurgery Oral surgery Orthopedic Plastic surgery Radiology Urology Procedure timing Elective Emergent Unknown Anesthesia induction method Intravenous Inhaled Other Unknown
February 2014 • Volume 118 • Number 2
Middle (n = 163)
Oldest (n = 66)
n 26 9
% 74.3 25.7
n 108 54
% 66.3 33.1
n 55 11
% 83.3 16.7
P 0.04
22 8 0 3 1 0 0 0 0 1
62.9 22.9 0.0 8.6 2.9 0.0 0.0 0.0 0.0 2.9
119 16 1 14 2 0 2 3 2 4
73.0 9.8 0.6 8.6 1.2 0.0 1.2 1.8 1.2 2.5
44 5 2 12 0 1 0 2 0 0
66.7 7.6 3.0 18.2 0.0 1.5 0.0 3.0 0.0 0.0
0.19
4 0 1 2 0 1 0 1 9
11.4 0.0 2.9 5.7 0.0 2.9 0.0 2.9 25.7
5 0 5 4 1 3 1 9 26
3.1 0.0 3.1 2.5 0.6 1.8 0.6 5.5 16.0
4 1 2 2 3 4 1 3 14
6.1 1.5 3.0 3.0 4.5 6.1 1.5 4.5 21.2
0.09 0.38 1 0.51 0.1 0.19 0.62 1 0.33
1 3 3 0 0 1 0 5 0 3 1 0 0 0 0
2.9 8.6 8.6 0.0 0.0 2.9 0.0 14.3 0.0 8.6 2.9 0.0 0.0 0.0 0.0
6 9 3 6 7 10 2 9 2 3 6 0 4 3 2
3.7 5.5 1.8 3.7 4.3 6.1 1.2 5.5 1.2 1.8 3.7 0.0 2.5 1.8 1.2
1 0 1 0 2 2 0 1 0 0 3 2 1 0 1
1.5 0.0 1.5 0.0 3.0 3.0 0.0 1.5 0.0 0.0 4.5 3.0 1.5 0.0 1.5
0.87 0.05 0.07 0.26 0.63 0.64 1 0.04 1 0.04 0.9 0.08 1 0.71 1
2 1 8 1 7 0 1 0 2 2 1 10
5.7 2.9 22.9 2.9 20.0 0.0 2.9 0.0 5.7 5.7 2.9 28.6
2 22 63 7 11 0 4 4 21 9 0 10
1.2 13.5 38.7 4.3 6.7 0.0 2.5 2.5 12.9 5.5 0.0 6.1
0 0 6 3 9 1 1 4 33 4 0 2
0.0 0.0 9.1 4.5 13.6 1.5 1.5 6.1 50.0 6.1 0.0 3.0
0.14 0.001
Malignant Hyperthermia in Children: An Analysis of the North American Malignant Hyperthermia Registry Priscilla Nelson, MD, and Ronald S. Litman, DO BACKGROUND: Clinical characteristics of malignant hyperthermia (MH) in pediatric patients have not been elucidated. In this study, we used the North American Malignant Hyperthermia Registry to determine differences in clinical characteristics of acute MH across pediatric age groups. We hypothesized that there are differences in clinical presentation, clinical course, and outcomes, which correlate with age. A secondary aim was to determine the types of preexisting medical conditions associated with pediatric MH. METHODS: We performed a retrospective review of the North American Malignant Hyperthermia Registry to identify pediatric subjects (up to and including 18 years) with an MH clinical grading score at or above 35 indicating “very likely” or “almost certain” MH. Preoperative patient characteristics, perianesthetic factors, and outcome data were compared for 3 cohorts based on age: 0 to 24 months, 25 months to 12 years, and 13 to 18 years. We used statistical analysis to determine differences among the groups. RESULTS: We analyzed 264 records: 35 in the youngest age group, 163 in the middle age group, and 66 in the oldest group. There was no indication of any predisposing risk factors for MH based on family history or physical examination. Sinus tachycardia, hypercarbia, and rapid temperature increase were the most common signs of acute MH (observed in 73.1%, 68.6%, and 48.5%, respectively) and were more common in the oldest age cohort. Higher maximum temperatures and higher peak potassium values were seen in the oldest age cohort. Masseter spasm was more common in the middle age cohort. The youngest age cohort was more likely to develop skin mottling and was approximately half as likely to develop muscle rigidity. The youngest age group also demonstrated significantly higher peak lactic acid levels and lower peak creatine kinase values. Treatments were similar across age cohorts. There were 10 MH-associated deaths, 6 in the middle age group and 4 in the oldest age group. Recrudescence of symptoms after initial treatment occurred in 14.4% of subjects, with no difference across age cohorts. Two of these subjects, 1 in the middle age group and 1 in the oldest age group, died after the recrudescence event. CONCLUSIONS: There are differences in clinical characteristics of acute MH among different age cohorts in childhood. Older subjects demonstrated higher body temperatures and higher potassium levels, and the youngest subjects had greater levels of metabolic acidosis. Most children in each age group were phenotypically normal before developing MH. (Anesth Analg 2014;118:369–74)
A
pproximately 17% of cases of malignant hyperthermia (MH) occur in children,1 yet the clinical characteristics of MH in the pediatric population have not been fully elucidated. Gaps in knowledge include preoperative risk stratification as well as clinical presentations and responses to treatment that are unique to children based on developmental age.
From the Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Accepted for publication August 7, 2013. Funding: Departmental sources only: Children’s Anesthesia Associates. The authors declare no conflicts of interest. This report was previously presented, in part, at the Annual meeting of the American Society of Anesthesiologists, Washington, DC, October 2012. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.anesthesia-analgesia.org). Reprints will not be available from the authors. Address correspondence to Ronald S. Litman, DO, Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, 34th St., Civic Center Blvd, Philadelphia, PA 19104. Address e-mail to [email protected]. Copyright © 2013 International Anesthesia Research Society DOI: 10.1213/ANE.0b013e3182a8fad0
February 2014 • Volume 118 • Number 2
The primary aim of this study was to use data from the North American Malignant Hyperthermia Registry (NAMHR)2,3 to determine the differences in clinical characteristics of acute MH across pediatric age populations. Given the developmental changes in body structure and composition throughout childhood, we hypothesized that there are differences in clinical presentation, clinical course, and outcomes based on the age group of the patient. A secondary aim was to determine the types of preexisting medical conditions that were associated with pediatric MH cases.
METHODS
We obtained permission from the IRB of the Stokes Research Institute of The Children’s Hospital of Philadelphia (requirement for written consent was waived by the IRB because the database was de-identified at its source) to conduct a retrospective analysis of all subjects up to and including 18 years of age in the NAMHR with an MH clinical grading scale (CGS) score at or above 35, indicating “very likely” or “almost certain” MH. The CGS represents a qualitative score of the likelihood that an MH event occurred, on the basis of clinical characteristics and laboratory results.4 www.anesthesia-analgesia.org
369
Malignant Hyperthermia in Children
The NAMHR database is divided into 3 general categories of data that correspond to the data fields of the Adverse Metabolic or Muscular Reaction to Anesthesia (AMRA) Report (Appendix, see Supplemental Digital Content 1, http://links.lww.com/AA/A601): (1) preoperative patient demographics and risk factors; (2) clinical characteristics of the acute MH event; and (3) postevent clinical characteristics and outcomes. The database was supplied to us in an Excel spreadsheet format (Microsoft, Redwood, WA).
Statistical Analyses
To test our hypotheses, we divided eligible subjects into 3 agebased cohorts: 0 to 24 months (youngest age group), 25 months to 12 years (middle age group), and 13 to 18 years (oldest age group). Comparisons of variables of interest among age cohorts were performed with Stata IC 10.1 (College Station, TX), using the Kruskal-Wallis test to analyze continuous variables and χ2 or Fisher exact test to compare categorical variables. Statistical significance was defined as P < 0.05.
RESULTS
There were 351 subjects aged 18 years and younger in the NAMHR, stemming from events that occurred between 1960 and 2011. When these records were subjected to a screen based on the MH CGS score, we obtained 264 (75.2%) records that met the criteria for MH as “very likely” or “almost certain.” Of these, 35 belonged to the youngest age group, 163 in the middle age group, and 66 in the oldest age group.
Preoperative Patient Demographics and Risk Factors
Most subjects in our cohort were male; although this predominance held across age cohorts, it was more pronounced in the oldest age group (P = 0.04) (Table 1). Most subjects were Caucasian; no significant differences were noted in racial composition among age groups. Although the youngest cohort trended towards a higher family history of MH (P = 0.09), there appeared to be no differences between the age groups with regard to family history of MH-related events or illnesses. Forty-nine subjects (18.5%) had a family history of MH or other MH-related illness, but this did not significantly differ by age group. The youngest age group trended toward being more likely to have generalized muscle weakness (P = 0.07) and was noted to have a higher incidence of undescended testes (P = 0.04) and inguinal hernia (P = 0.04). These differences are likely related to a surgical case-based bias. No difference was noted in the number of prior anesthetic procedures, but the MH event was the first procedure for 50% of patients and the second procedure for 20% (not shown in Table 1). The case type by service was distributed across specialties, with cases most commonly involving ear, nose, and throat (29%) and orthopedics (21.2%). The type of case was variable by age group, with urological cases accounting for nearly 30% of the youngest group events (P ≤ 0.001), earnose-throat cases accounting for nearly 40% of the middle group events (P ≤ 0.001), and orthopedic cases accounting for 50% of oldest cohort events (P ≤ 0.001). Cases for the youngest group were nearly all scheduled, while the adolescent cohort had a higher percentage of emergent procedures
370 www.anesthesia-analgesia.org
(P ≤ 0.001). Although denominators for non-MH cases are not available, these case distributions are likely reflective of a typical case distribution in children by age group. Most children had induction of general anesthesia with IV drugs, although the youngest group was more likely to receive an inhaled induction (P = 0.003). As expected, IV induction was significantly associated with emergent cases (97.4% vs 80.9%, P = 0.009). The youngest age group was less likely to receive IV succinylcholine (P ≤ 0.001), vecuronium (P = 0.001), propofol (P ≤ 0.001), or fentanyl (P < 0.001) but was more likely to receive halothane (P < 0.001) or sevoflurane (P = 0.013) compared with the older cohorts. These results are also likely explained by normal age-based clinical practice.
Event Characteristics
Sinus tachycardia, hypercarbia, and rapid temperature increase were the most commonly observed physical examination findings (observed in 73.1%, 68.6%, and 48.5%, respectively) (Table 2); the oldest cohort was more likely to develop these findings. The oldest age group took longer to reach their maximum end-tidal CO2 value, had higher peak potassium values, and was more likely to demonstrate sweating during the event. The middle age cohort had a lower maximum end-tidal CO2 and blood gas Pco2 compared with the youngest and oldest age groups. The middle age cohort was more likely to develop masseter spasm, and the youngest age cohort was more likely to develop skin mottling. Although no significant differences were noted in the incidence of generalized muscle rigidity, dark colored urine, tachypnea, cyanosis, ventricular arrhythmias, or overall temperature increase among age groups, the youngest age cohort was approximately half as likely to demonstrate muscle rigidity. Masseter spasm was significantly more common in children who received succinylcholine (75/125 vs 11/128, P < 0.001). However, there were differences when analyzed separately by age group. For example, although infrequently used in subjects in the youngest age group, masseter spasm and subsequent MH occurred in 4 of the 5 subjects in this age group who received succinylcholine. In the oldest age group, there was no significant difference in appearance of masseter spasm between the subjects who did and did not receive succinylcholine (P = 0.17). Subjects in the oldest age cohort reached a higher maximum temperature compared with those in the youngest and middle cohorts; subjects in the youngest age group tended to take longer to reach their maximum value (P = 0.07), and they tended to have a lower blood pH (P = 0.06). Subjects in the youngest age group also demonstrated significantly higher peak lactic acid levels (P = 0.0025) and lower peak creatine kinase (P ≤ 0.001) values.
Treatments and Outcomes
For nearly all treatments, regimens were similar across age cohorts. The oldest age cohort was more likely to receive active cooling (they had higher temperatures) and fluid administration (Table 3). The older cohort more commonly received glucose and insulin in their treatment, which likely related to their higher potassium values. Dantrolene was administered in >73% of events, with the average initial and
anesthesia & analgesia
Table 1. Patient Demographics and Procedural Characteristics Youngest (n = 35) Characteristic Male Female Race Caucasian Hispanic African American Native American Hawaiian/Pacific islander African East Asian South Asian Middle Eastern Other race not listed Family history Malignant hyperthermia Masseter rigidity Intraoperative event Sudden infant death syndrome Sudden death Heat stroke Heat intolerance Myopathy Any family history (from the above) Physical exam findings Increased muscle tone Decreased muscle tone General muscle weakness Myopathy Ptosis Strabismus Hiatal hernia Inguinal hernia Umbilical hernia Undescended testicles Clubbed foot Joint hypermobility Kyphoscoliosis Winged scapulae Skeletal fractures Case type Cardiothoracic Dental Ear, nose, and throat Ophthalmology General surgery Gynecology Neurosurgery Oral surgery Orthopedic Plastic surgery Radiology Urology Procedure timing Elective Emergent Unknown Anesthesia induction method Intravenous Inhaled Other Unknown
February 2014 • Volume 118 • Number 2
Middle (n = 163)
Oldest (n = 66)
n 26 9
% 74.3 25.7
n 108 54
% 66.3 33.1
n 55 11
% 83.3 16.7
P 0.04
22 8 0 3 1 0 0 0 0 1
62.9 22.9 0.0 8.6 2.9 0.0 0.0 0.0 0.0 2.9
119 16 1 14 2 0 2 3 2 4
73.0 9.8 0.6 8.6 1.2 0.0 1.2 1.8 1.2 2.5
44 5 2 12 0 1 0 2 0 0
66.7 7.6 3.0 18.2 0.0 1.5 0.0 3.0 0.0 0.0
0.19
4 0 1 2 0 1 0 1 9
11.4 0.0 2.9 5.7 0.0 2.9 0.0 2.9 25.7
5 0 5 4 1 3 1 9 26
3.1 0.0 3.1 2.5 0.6 1.8 0.6 5.5 16.0
4 1 2 2 3 4 1 3 14
6.1 1.5 3.0 3.0 4.5 6.1 1.5 4.5 21.2
0.09 0.38 1 0.51 0.1 0.19 0.62 1 0.33
1 3 3 0 0 1 0 5 0 3 1 0 0 0 0
2.9 8.6 8.6 0.0 0.0 2.9 0.0 14.3 0.0 8.6 2.9 0.0 0.0 0.0 0.0
6 9 3 6 7 10 2 9 2 3 6 0 4 3 2
3.7 5.5 1.8 3.7 4.3 6.1 1.2 5.5 1.2 1.8 3.7 0.0 2.5 1.8 1.2
1 0 1 0 2 2 0 1 0 0 3 2 1 0 1
1.5 0.0 1.5 0.0 3.0 3.0 0.0 1.5 0.0 0.0 4.5 3.0 1.5 0.0 1.5
0.87 0.05 0.07 0.26 0.63 0.64 1 0.04 1 0.04 0.9 0.08 1 0.71 1
2 1 8 1 7 0 1 0 2 2 1 10
5.7 2.9 22.9 2.9 20.0 0.0 2.9 0.0 5.7 5.7 2.9 28.6
2 22 63 7 11 0 4 4 21 9 0 10
1.2 13.5 38.7 4.3 6.7 0.0 2.5 2.5 12.9 5.5 0.0 6.1
0 0 6 3 9 1 1 4 33 4 0 2
0.0 0.0 9.1 4.5 13.6 1.5 1.5 6.1 50.0 6.1 0.0 3.0
0.14 0.001
