Elevated Serum Creatine Phosphokinase Research Articles

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Benign acute childhood myositis: Factors associated with muscle symptoms and resolution.

Benign acute childhood myositis (BACM) is associated with several viral infections. The aim of this study was to evaluate the progression of myositis symptoms, laboratory findings and oseltamivir treatment in children with influenza- and non-influenza-associated BACM. Patients aged 0-18 years old, admitted to the pediatric emergency department in the seasonal influenza period between 2018 and 2020 were retrospectively analyzed. Patients with acute onset calf tenderness, pain, difficulty in walking and elevated serum creatine phosphokinase were included and were grouped according to influenza rapid test kit results as influenza (A and B) positive, and influenza negative. The time to symptom resolution, laboratory data and the oseltamivir treatment were compared between the groups. There were 94 patients (67 male, 27 female) with a mean age of 77 ± 22 months. Influenza A was detected in 21, influenza B in 27, and neither were detected in 46 patients. Time to symptom resolution of BACM was shorter in the influenza-positive patients than in influenza-negative patients (2.9 ± 1.4 days and 3.5 ± 1.5 days, respectively, P = 0.027). Oseltamivir did not reduce the symptom resolution time in influenza patients. All children had normal hemoglobin and platelet counts, elevated creatine phosphokinase and 76% of them had leukopenia. Neither clinical recurrence nor metabolic disease were reported. Symptoms of BACM tended to resolve slightly earlier in influenza-positive patients and the duration of symptoms was not affected by oseltamivir treatment.

A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature

BackgroundVery long-chain acyl-coenzyme-A dehydrogenase deficiency is a rare, severe life-threatening metabolic disorder of mitochondrial fatty acid oxidation, caused by mutations in ACADVL gene. Here we present a genetically confirmed case of a South Asian baby girl with severe, early-onset form of very long-chain acyl-coenzyme-A dehydrogenase deficiency due to a novel mutation in ACADVL gene.Case presentationIndex case was the second baby girl of second-degree consanguineous South Asian parents. She had an uncomplicated antenatal period and was born by spontaneous vaginal delivery at term with a birth weight of 2910 g. She had been noted to have fair skin complexion, hypotonia, and 3 cm firm hepatomegaly. Since birth, the baby developed grunting, poor feeding, and recurrent episodes of symptomatic hypoglycemia and convulsions with multiple semiology. Her septic screening and urine ketone bodies were negative. The baby had high anion gap metabolic acidosis and elevated transaminases and serum creatine phosphokinase levels. Echocardiogram at 4 months revealed bilateral ventricular hypertrophy. Acylcarnitine profile revealed elevated concentrations of tetradecanoylcarnitine (C14), tetradecanoylcarnitine C14:1, and C14:1/C16. Unfortunately, the baby died due to intercurrent respiratory illness at 4 months of age. Sequence analysis of ACADVL gene in perimortem blood sample revealed homozygous frame shift novel variant NM_001270447.1, c.711_712del p.(Phe237Leufs*38), which confirmed the diagnosis of very long-chain acyl-coenzyme-A dehydrogenase deficiency.ConclusionsThis case demonstrates the importance of early diagnosis and management of very long-chain acyl-coenzyme-A dehydrogenase deficiency in improving the outcome of the patients. Implementation of newborn screening using tandem mass spectrometry in Sri Lanka will be beneficial to reduce the morbidity and mortality of treatable disorders of inborn errors.

Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature.

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

Safety and efficacy of HX008: A humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma—A single-arm, multicenter, phase II study.

9554 Background: HX008 is a new recombinant humanized anti-PD-1 monoclonal antibody, belonging to human IgG4 / kappa subtype, which can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods: In this single arm phase 2 trial, eligible patients (pts) were aged from18 to 75, who previously failed with conventional treatment for locally advanced or metastatic melanoma, with an ECOG performance status of 0 or 1 and had measurable lesions according to the RECIST criteria (V1.1). Ocular melanoma, brain metastasis or previous use of anti PD-1 ab were excluded. Pts received HX008 3mg/kg every 3 weeks, until disease progression, intolerable toxicity or treatment discontinuation for any other reasons. The primary endpoint was ORR according to RECIST criteria, and the secondary endpoints were OS, PFS, DCR and the toxicity. The iRECIST criteria would also be used in the evaluation of response and treatment discontinuation. Clinical trial information: NCT04749485. Results: From Oct 2018 to Jan 2021, 119 pts have been eligible and enrolled. Basic characteristics: median age 59 years; 57 males (42.9%) ; stage 22%, stage 78%; primary: acral 52.1%, mucosal 19.3%, cutaneous 18.5% and unknown 10.1%; Gene mutation status: Braf 10.9%, Nras 9.2%, cKit 4.2%; condition of previous treatments: 67.26%, 25.21%,7.56% pts had received 1st, 2nd and 3rd line or above treatments respectively (chemotherapy 69.7%, targeted therapy 15.1%, immunotherapy 43.7%). The ORR according to RECIST V1.1 and iRECIST was 18.49% (1CR, 21 PR, 95% CI 11.96-26.64) and 20.17% (1 iCR, 23 iPR,95% CI 13.37-28.50), respectively. For PD-L1 positive pts the ORR was 15.09% (95%CI 6.75-27.60) and 12% for negative (95%CI 10.98-32.83). For different subtypes, the ORR was 36.36% for cutaneous melanoma, 14.52% for acral primary, 8.7% for mucosal primary, and 25% for unknown primary. The DCR and iDCR was 44.54% and 47.06%, respectively. With a median follow up time of 13.2 months, the median PFS was 3.25 months (95% CI 2.0, 4.1) and the PFS rate at 1 year was 25.8% (95%CI 17.19,35.33). The median OS was 17.91 months (95% CI 13.08,NR) and the OS rates at 1 year was 63.9% (95% CI 53.02, 73.00). Median DOR has not reached and the DOR and iDOR rates at 1 year were 80.64% and 87.39%, respectively. TRAEs occurred in 89.9% of the pts, with grade 3/4 AEs 31.9%, the followings were those incidences ≥1%, hyperglycemia (2.5%), elevated aspartate aminotransferase (1.7%), elevated serum bilirubin (1.7%), elevated serum creatine phosphokinase (1.7%), elevated lipase (1.7%), hypoalbuminemia (1.7%), hypokalemia (1.7%) and diabetic ketoacidosis (1.7%). Conclusions: HX008 shows its efficacy and safety in locally advanced or metastatic melanoma pts in the treatments of 2nd line or above. Randomized controlled studies are now on pending. Clinical trial information: NCT04749485.

Effects of soy isoflavone on cardiac dysfunction in geripause-like rats: comparisons with hormone-replacement therapy

Background Cardiovascular diseases are a primary cause of morbidity and mortality worldwide. The prevalence of cardiovascular disease as well as inflammation in postmenopausal women is higher than premenopausal women. Objective The present study investigated cardiac dysfunction elicited by estrogen deprivation and aging and assessed a possible beneficial impact of isoflavones compared with estradiol-replacement therapy. Materials and methods Forty aged female rats were equally divided into four groups. Except for sham-operated animals in group 1 (negative control), all other rats were ovariectomized. One month after surgery, animals were assigned to groups 3 and 4. Rats in the former group were treated with 17β-estradiol, 100 μg/kg, intramuscular, every other day. Animals in group 4 were administered soy isoflavones (SIF), 40 mg/kg/day orally. Treatments continued for 1 month. Results and conclusion Compared with control rats, ovariectomized animals showed cardiac dysfunction and inflammation evidenced by dyslipidemia and elevated serum creatine phosphokinase and lactate dehydrogenase activity, angiotensin II, cardiac malondialdehyde and nitric oxide levels, and serum tumor necrosis factor-α and interleukin-6 levels. These impacts were concurrent with significant decreases in cardiac catalase activity and total antioxidant capacity. Treatment with SIF was more effective in mitigating inflammation and cardiac dysfunction compared with estradiol-replacement therapy. Histopathological examination of heart tissues supports these biochemical findings. SIF are a safe and well-tolerated alternative to estradiol for improving cardiac dysfunction elicited by menopause and age.

A unique presentation of benign acute childhood myositis in a child withinfluenza B.

Benign Acute Childhood Myositis (BACM) is a syndrome of a self-limiting muscle disorder characterized by bilateral calf pain and difficulty in walking with an isolated finding of elevated serum Creatine Phosphokinase (CPK) and leukopenia preceded by influenza like illness. The symptoms of BACM tend to disappear within a week. The syndrome has classical clinical and laboratory features that may allow for a correct diagnosis. Herein we describe BACM in an 11-year old boy with recurrent tonsillitis associated with vague muscle aches and discovered to have vitamin D deficiency with hypocalcemia. He had unique features that include persistence of symptoms beyond a week, recurrent episodes per year, and a concurrent similar case in the family. Awareness of the symptom complex is important for early diagnosis and avoidance of unnecessary investigations and treatment.

Immune mediated necrotizing myopathy: A rare complication of statin therapy.

Immune mediated necrotizing myopathy (IMNM) is part of the inflammatory myopathies group of diseases and presents with muscle weakness, myalgias and elevated serum creatine phosphokinase (CPK). Statin-induced IMNM is a rare complication. We present a patient with IMNM secondary to simvastatin use. The patient presented with proximal myopathy, dysphagia, and elevated creatinine kinase levels, and was subsequently found to have anti-3- hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies with a necrotizing process on muscle biopsy. This patient’s case was further complicated by sequelae of multiple disease processes, ultimately leading to deterioration of his health.

Clinical and epidemiological descriptions from trichinellosis outbreaks in Bulgaria

Bulgaria is one of European countries where trichinellosis continues to be regularly diagnosed and registered. The clinical and epidemiological features of 72 cases of trichinellosis associated with five outbreaks caused by Trichinella spiralis and Trichinella britovi between 2009 and 2011, are described. At hospital admission, patients were often initially treated with antibiotics, without any improvement. A range of signs and symptoms were recorded, including: myalgia, elevated temperature, arthralgia, difficulty with movement, facial oedema, conjunctival hyperaemia, ocular haemorrhages, diarrhoea, skin rash, headache, and fatigue. Due to the variable clinical course of the disease, the diagnostic process for trichinellosis is often complex and difficult. This means the diagnosis may be established late for an appropriate treatment, potentially leading to a severe course of the disease with complications. Laboratory abnormalities were expressed by marked eosinophilia (97.2%), leucocytosis (70.8%), elevated serum creatine phosphokinase levels (82%), and antibody-positive results by ELISA and indirect hemagglutination. Patients were treated with albendazole (Zentel) 10 mg/kg for 7–10 days.In two outbreaks, the aetiological agent was T. spiralis, in one outbreak T. britovi, and an unknown Trichinella species in the fourth outbreak. The sources of infection were domestic pigs, probably fed with scraps and offal of wild game. In one outbreak, T. spiralis was also detected in brown rats trapped close to where the pig had been raised in the backyard. These epidemiological factors are relevant in considering implementation of targeted control programmes.

Alteration in Serum Creatine Phosphokinase in Hypothyroid Female Subjects of Reproductive Age Group in an Urban Population in Eastern India: A Cross Sectional Observational Study

Background: Serum creatine phosphokinase (CPK) acts as important clinical parameter in muscle damage. Hypothyroid subjects may have elevated serum CPK level but correlation of the two is not well established till date. Aims: To assess the significance of increased serum CPK level as biochemical tool in hypothyroidism in an urban young female population of reproductive age group in eastern India. Materials & methods: This cross sectional study was conducted on 200 hypothyroid subjects in Burdwan Medical College in a period of 12 months after taking Institutional Ethical Clearance.100 subjects were enrolled in the study as control. Serum TSH, FT4 and CPK levels were estimated. The subjects were age matched. The computer software SPSS, version 16.0 was used for analyzing data. Results: Among 200 hypothyroid subjects enrolled in the study, 50 hypothyroid patients had increased Serum CPK level (25%). Significant difference was observed between control and hypothyroid subjects for mean TSH (P<0.0001), mean FT4 (P<0.0001) and mean CPK (P<0.0001).Serum CPK level was positively correlated with TSH levels (r=0.761, P<0.00001) and Serum CPK was negatively correlated with Sr. FT4(r= -0.328; P<0.00001). Conclusions: It may be concluded from our study that Hypothyroid females in reproductive age group may have significant increase in serum CPK levels as compared to normal subjects and may be considered as important biochemical tool for the screening of muscle damage in hypothyroid individuals.

Retrospective case analysis of crayfish-transmitted Haff disease in China during 2016–2017

Haff disease is an unexplained rhabdomyolysis syndrome occurring within 24 h of consumption of certain types of cooked fish or crustaceans. The current epidemiological status of crayfish-transmitted Haff disease in China was investigated by analyzing retrospective data linked with cases of the rhabdomyolysis syndrome recorded during the period 2016–2017. This information was acquired from the National Foodborne Disease Surveillance and Reporting System. These data were filtered, based on the disease definition and a markedly elevated serum creatine phosphokinase level, that is, fivefold or greater increase than normal levels. Data analysis indicated that crayfish-transmitted Haff disease was mainly concentrated in the middle and lower reaches of the Yangtze River Valley, and the current epidemiological curve was notable seasonal. Most patients were aged 20–49 years and the proportion of female patients was higher than male patients. Based on this initial study, it will be necessary to follow up the trace-back investigation of crayfish poisoning reports; further analyze the correlation between the aquatic environment of the associated crayfish together with establishing virulence factors of crayfish-transmitted Haff disease; and explore whether certain individuals have receptor pathways to trigger rhabdomyolysis syndrome.

Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis

Objectives: Subcutaneous involvement, including calcinosis and panniculitis, is a more common complication in juvenile dermatomyositis (JDM) than in adult dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating disease distribution. We investigated the clinical significance of subcutaneous involvement in JDM.Methods: Thighs and hips in 18 newly diagnosed JDM patients were evaluated with fat-suppression MRI. Bilateral muscle, fascial and subcutaneous fat involvement were scored from 0 to 8 points according to the severity of distribution on MRI. Associations between clinical manifestations, serum muscle enzymes, and MRI scores were also evaluated.Results: Abnormal MRI findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10 patients, respectively. Subcutaneous fat scores were significantly higher in early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in late-diagnosed JDM patients (diagnosed later) (p = .025). Serum aldolase was elevated in all patients, although only eight demonstrated elevated serum creatine phosphokinase. Serum aldolase was significantly correlated with MRI scores for subcutaneous fat (p < .0001, ρ = .787) and fascia (p = .013 ρ = 0.574), but not muscle. Additionally, serum aldolase was significantly correlated with serum triglycerides (p = .009, ρ = 0.629).Conclusion: Subcutaneous fat involvement is a characteristic finding in early-diagnosed JDM and correlates with elevated serum aldolase.

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B

BackgroundCurrent treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment.Case presentationThe patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 μmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range.ConclusionsThis case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.

Severe non-exertional rhabdomyolysis from weight loss supplement in sickle cell trait: A perfect storm?

Exertional rhabdomyolysis from sickle cell trait has been documented. Also, cases of rhabdomyolysis from the use of weight loss supplements in the setting of sickle cell trait and exertion have been described. However, the role of sickle cell trait in non-exertional rhabdomyolysis is not clear. We present a case of severe non-exertional rhabdomyolysis from weight loss supplement in a patient with sickle cell trait.A 45-year-old African American female with sickle cell trait presented to the emergency department with two days history of fatigue and mild breathlessness. She also reported diarrhea and vomiting for five days before presentation. She admitted to taking Garcinia cambogia (a dietary supplement) for weight loss one week prior to the onset of symptoms. She denied alcohol or drug use, rigorous physical activity or trauma.She was dehydrated on examination. Laboratory values revealed markedly elevated serum creatine phosphokinase (CPK) and creatinine levels. Garcinia cambogia was discontinued and she was hydrated with intravenous fluids. Her CPK and creatinine levels significantly trended down and she was discharged home with no apparent sequelae.Our patient had multiple episodes of diarrhea and vomiting likely from the use of Garcinia cambogia. We believe she suffered non-exertional rhabdomyolysis from dehydration in the setting of sickle cell trait. Though dietary weight loss supplements are marketed as generally safe, this case suggests otherwise. We emphasize that clinicians routinely inquire about use of these supplements and provide appropriate counseling to patients on the adverse effects, especially among those with sickle cell trait.

A rare subclinical or mild type of Becker muscular dystrophy caused by a single exon 48 deletion of the dystrophin gene

In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation—a single exon 48 deletion of the dystrophin gene—who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered.

A Multidisciplinary Evaluation Helps Identify the Antisynthetase Syndrome in Patients Presenting as Idiopathic Interstitial Pneumonia.

Interstitial lung disease (ILD) is 1 possible manifestation of the idiopathic inflammatory myopathies (IIM). Occasionally, patients presenting with ILD are mistakenly diagnosed with idiopathic interstitial pneumonia (IIP), but after multidisciplinary evaluation, their ILD is determined to be because of antisynthetase syndrome (SynS) or myositis spectrum of disease. We used retrospective analytic methods to identify patients with ILD evaluated at the National Jewish Health between February 2008 and August 2014 and believed initially to have IIP but ultimately diagnosed with SynS or myositis spectrum of disease. The cohort included 33 patients; most were white women with a mean age at presentation of 55 years. Their pulmonary physiologic impairment was moderate. In 31 cases, the ILD pattern by thoracic high-resolution computed tomography scan was nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), or a combination of the 2. Surgical lung biopsy was performed in 21 patients; NSIP was the most common pattern. Less than one-third of the cohort had positive antinuclear antibodies. Two-thirds had positive SSA. All patients had either myositis-specific or myositis-associated autoantibody. Most had subtle extrathoracic symptoms or signs of SynS; 12 had an elevated serum creatine phosphokinase, but none had clinical evidence of myositis. None met the Peter and Bohan classification criteria for polymyositis/dermatomyositis. Among patients who present with presumed IIP, a multidisciplinary evaluation that includes the integration of clinical evaluations by rheumatologists and pulmonologists, morphologic (both histopathologic and radiographic) data, and serologic features is helpful in the detection of occult SynS or the myositis spectrum of disease.

Neuroleptic Malignant Syndrome: A Case Aimed at Raising Clinical Awareness

A 60-year-old man with a history of bipolar disorder on risperidone, bupropion, and escitalopram was admitted for community acquired streptococcal pneumonia. Four days later, he developed persistent hyperthermia, dysautonomia, rigidity, hyporeflexia, and marked elevation of serum creatine phosphokinase. He was diagnosed with neuroleptic malignant syndrome (NMS) and improved with dantrolene, bromocriptine, and supportive therapy. This case emphasizes the importance of considering a broad differential diagnosis for fever in the ICU, carefully reviewing the medication list for all patients, and considering NMS in patients with fever and rigidity.

Amlodipine intoxication complicated by acute kidney injury and rhabdomyolysis

Amlodipine, a calcium channel blocker of the dihydropyridine group, is commonly used in management of hypertension, angina, and myocardial infarction. Amlodipine overdose, characterized by severe hypotension, arrythmias, and pulmonary edema, has seldom been reported in Korean literature. We report on a fatal case of amlodipine intoxication with complications including rhabdomyolysis and oliguric acute kidney injury. A 70-year-old woman with a medical history of hypertension was presented at the author's hospital 6 hours after ingestion of 50 amlodipine (norvasc) tablets (total dosage 250 mg) in an attempted suicide. Her laboratory tests showed a serum creatinine level of 2.5 mg/dL, with elevated serum creatine phosphokinase and myoglobin. The patient was initially treated with fluids, alkali, calcium gluconate, glucagon, and vasopressors without a hemodynamic effect. High-dose insulin therapy was also started with a bolus injection of regular insulin (RI), followed by continuous infusion of RI and 50% dextrose with water. Despite intensive treatment including insulin therapy, inotropics, mechanical ventilation, and continuous venovenous hemodiafiltration, the patient died of refractory shock and cardiac arrest with no signs of renal recovery 116 hours after her hospital admission.

Predicting the intermediate syndrome in organophosphorus poisoning.

Intentional organophosphorus (OP) poisoning is estimated to kill between 230,000 and 350,000 people a year worldwide, with a further 20,000 dying following accidental exposure.[1] The occurrence of a “type II paralysis,” usually proximal muscle paralysis, in survivors after the resolution of cholinergic features was recognized as complicating up to 18% of OP related admissions during an early case-series.[2] Senanayake and Karalliedde[3] classified this paralysis as the “intermediate syndrome” and described it as a distinct clinical entity on the basis of electromyographic (EMG) evidence of postsynaptic neuromuscular junction (NMJ) failure that occurred between 24 and 96 h after the resolution of the cholinergic crisis and prior to the onset expected for delayed neuropathy. The respiratory muscles are often affected and a prolonged period of ventilator support is required with all the associated risks of clinical complications and healthcare costs that such treatment entails. The pathophysiological mechanism of the syndrome remains obscure and empirical data are limited, although oxidative stress and changes in receptor-ligand binding kinetics have been reported. Muscle biopsies taken during the Bleecker et al. case series reported a limited degree of fiber necrosis that was considered to be insufficient to account for the clinical features observed during the study.[4] Biomarkers of oxidative stress, at least in erythrocytes, have been identified in patients with the intermediate syndrome.[5] A rat model of dimethoate poisoning described changes in skeletal muscle and lymphocyte, but not the central nervous system, nicotinic receptor binding function 48 h postexposure.[6] Several risk factors have been proposed for the development of intermediate syndrome. The type of OP and the severity of poisoning may be important. In a small prospective case series (n = 19, eight of which developed intermediate syndrome), Bleecker et al.,[4] noted that dimethyl OP agents were more commonly implicated in comparison with diethyl OP compounds. An observation later confirmed by Indira et al.[7] Bleecker et al.,[4] also observed that the clinical features and recovery correlated closely with EMG features and hypothesized that the NMJ dysfunction related to both pre- and post-synaptic changes. The degree of acetylcholinesterase inhibition has also found to be greater in individuals who went on to develop the syndrome.[4] The 1st day serum acetylcholinesterase activity does not, however, appear to predict the onset of the intermediate syndrome but may predict survival.[8] A finding not inconsistent with the observations reporting by Indira et al.,[7] of an increased relative risk of the intermediate syndrome in patients with a higher poisons severity score or reduced Glasgow Coma Scale. In this edition of the Journal, a prospective observational study by Kumar et al.[9] reported a significant rise in serum creatine phosphokinase (CPK) on admission and again, 48 h postadmission in three individuals with OP poisoning who subsequently developed intermediate syndrome compared to 72 h with OP poisoning who did not. Serum CPK concentrations were also noted to correlate with markers of poisoning severity such as the Peradeniya organophosphorus poisoning score, and the total dose of atropine administered, and inversely correlated with the degree of butyrylcholinesterase activity. These findings are consistent with those of Bhattacharyya et al.[10] who also described a correlation between admission CPK; the severity of poisoning and the risk of developing the intermediate syndrome. The study by Kumar et al.[9] has several strengths: The diagnosis of OP exposure was confirmed by cholinesterase activity measurement in each case; a standard treatment protocol was adhered to and the investigators excluded for the potential confounders that may cause an elevated serum CPK concentration, like seizures. The sample size of 75 makes this one of the larger studies focusing on the intermediate syndrome. The actual number of individuals who developed the syndrome was small. The authors acknowledge this limitation and note that this was due to the exclusion of those with severe poisoning. It remains unclear, therefore, if CPK is truly an independent risk factor for the intermediate syndrome or, instead, reflects disease severity; which in turn may be the principle risk factor for the onset of the syndrome. Determining the relative contributions of these and other potential risk factors for intermediate syndrome will require more research. A predictive test to risk-stratify those most likely to develop the syndrome is, however, a goal worth pursuing. If a successful test can be validated, using a resource that is readily available in the majority of healthcare settings then it should considerably aid the early identification of patients who are likely to require transfer to a center that can provide ventilator support over several days duration and also may facilitate further research into preventative therapies. The authors are to be commended for undertaking research into this problem, which is highly prevalent and disproportionately affects the more socioeconomically disadvantaged in our community. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Elevated serum creatine phosphokinase is associated with mortality and inotropic requirement in critically injured adults

BackgroundHemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients. MethodsWe conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support. ResultsMedian CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p=0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p<0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p=0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p<0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p<0.001) that remained significant in a propensity score-adjusted model. ConclusionIn critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.