Severe caffeine poisoning treated with intermittent hemodialysis under circulatory support.

Caffeine poisoning can cause fatal ventricular arrhythmias. In this report, we describe a case of severe caffeine poisoning with extraordinarily high blood caffeine levels. Despite developing refractory ventricular fibrillation, the patient was successfully treated with intermittent hemodialysis (IHD) under circulatory support by venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 22-year-old male was transported to our hospital approximately 2.5 h after ingesting 200 highly caffeinated tablets (200 mg/tablet) (40 g caffeine total) in a suicide attempt. On arrival, the patient vomited frequently with a Glasgow Coma Scale score E3V2M5, heart rate 185 beats/min, and a blood pressure of 97/62 mmHg. Shortly after arrival, the patient developed ventricular fibrillation which was refractory either to three electrical defibrillations or antiarrhythmic drugs, resulting in endotracheal intubation for mechanical ventilation and VA-ECMO. Starting from 2 h after arrival, intermittent hemodialysis (IHD) was performed for 11 h, which markedly improved clinical symptoms and circulatory parameters. Serum caffeine level was 454.9 mg/dL upon arrival at the hospital, but it decreased to 55.5 mg/dL by the end of IHD treatment. Renal replacement therapy (RRT) including intermittent hemodiafiltration, continuous hemodiafiltration, and IHD was continued because of rhabdomyolysis with myoglobinuria and secondary caused acute kidney injury. The patient was weaned off VA-ECMO on hospital day 7, extubated on hospital day 18, weaned from RRT on hospital day 46, and was transferred to another hospital for physical rehabilitation on hospital day 113. IHD under circulatory support by VA-ECMO should be considered in severe caffeine poisoning causing potentially fatal arrhythmias.

A suicide attempt by intramuscular injection of pentobarbital sodium into rectus abdominis suggested by computed tomography.

Suicide attempts in humans due to injections of the veterinary drug pentobarbital sodium have been rarely reported. Herein, we present a case of a suicide attempt by intramuscular injection of pentobarbital sodium into the rectus abdominis muscle, which was suggested by computed tomography (CT). A 73-year-old man was brought to the emergency department with GCS 3 (E1V1M1) and an incised wound on the right side of the neck. A bottle of Somnopentyl® (pentobarbital sodium, 64.8 mg/ml), a 20-ml empty syringe with an 18-mm needle, and no. 10 scalpel were present at the scene. At the emergency department, the patient was intubated and was admitted to the intensive care unit. A urine drug screen test by SIGNIFY® ER was positive for benzodiazepines and barbiturates, and continuous veno-venous hemofiltration (CHF) was initiated. The route of drug administration was initially unknown; however, a CT scan revealed swelling of the left rectus abdominis muscle with a wound suggestive of a needle puncture, and the CT analysis suggested 38.16 ml as the maximum dose of pentobarbital sodium. On day 3, the patient's consciousness improved, and he was weaned off CHF and mechanical ventilation. There have been several reports of postmortem CT yielding information on the site of administration of intoxicants, but there have been none for surviving intoxicated patients. This is the first report of the usefulness of CT to identify the site of administration of the causative agent of intoxication while the patient is still alive.

Total Hip Arthroplasty After Failed Hip-Preserving Surgery with Concentrated Autologous Bone Marrow Aspirate Transplantation for Osteonecrosis of the Femoral Head: A Retrospective Study.

Purpose: Since 2003, a hip-preserving technique-concentrated autologous bone marrow aspirate transplantation (CABMAT)-has been applied to treat osteonecrosis of the femoral head (ONFH). We investigated intraoperative and postoperative outcomes of total hip arthroplasty (THA) in patients who underwent CABMAT as hip-preserving surgery for ONFH but developed secondary hip osteoarthritis after progressive femoral head collapse. Methods: A total of 456 hips in 282 patients underwent CABMAT in our hospital between April 2003 and December 2018; 108 hips required THA (THA conversion rate, 23.7%). We enrolled 60 hips (26 hips in 20 men and 34 in 26 women) with a follow-up of over 2 years. We retrospectively analyzed patient background data, time to THA, surgical procedure, postoperative complications, and clinical outcomes from medical records. Results: The disease was steroid-related, alcohol-related, and idiopathic in 48, seven, and five hips, respectively. The mean age at THA was 45.7 years, and mean conversion time was 2.7 years. Cementless THA was performed in all cases; the mean operating time and blood loss were 82.7 min and 210 g, respectively. Postoperative complications were observed in four cases; intraoperative fracture, two cases; superficial infection, one case; and dislocation, one case. The mean follow-up period was 5.7 years; no loosening or deep infections occurred. No patients required revision arthroplasty. Conclusion: We noted no complications related to CABMAT. After a minimum 2-year follow-up, the clinical outcomes were good. CABMAT was found to be an useful hip-preserving surgery, with little effect on conversion to THA, and THA outcomes were good.

Severe caffeine poisoning successfully treated with high flow continuous hemodialysis.

In recent years, severe or lethal cases of caffeine poisoning after large or massive ingestion of caffeinated tablets have increased in Japan. Here we report the case of a 23-year-old male who ingested high-dose caffeine tablets (total: 32.4 g caffeine) in a suicide attempt. He was transferred to our hospital about 2 h after ingesting the tablets and presented with repeated vomiting and tremor in the trunk and extremities. His respiratory rate was 40 breaths/min, heart rate 240 beats/min, blood pressure 109/77 mmHg, and Glasgow Coma Scale E3V2M5. Blood tests revealed metabolic acidosis compensated with respiratory alkalosis, hyperlactatemia, hypokalemia, hyperglycemia, and leukocytosis. After tracheal intubation, gastric lavage was performed and activated charcoal was administered. The patient gradually became hypotensive (systolic blood pressure < 90 mmHg) with a heart rate > 250 beats/min, and non-sustained ventricular tachycardia frequently occurred. Given the lack of response to intravenous noradrenaline and landiolol, high flow continuous hemodialysis (CHD) was initiated 4 h after tablet ingestion with a blood flow rate of 150 mL/min and dialysate flow rate of 2000 mL/h. This dramatically improved his clinical signs and symptoms, especially during the first 3 h. His serum caffeine concentration was 240.9 µg/mL on admission and 344.0 µg/mL at the initiation of high flow CHD, but rapidly decreased to 153.8 µg/mL 3 h after initiating high flow CHD. Our findings suggest that high flow CHD may be effective in treating cases of severe caffeine poisoning with hemodynamics too unstable for intermittent hemodialysis.

Effectiveness of multiple-dose activated charcoal in lamotrigine poisoning: a case series.

INTRODUCTION: Lamotrigine toxicity can cause coma, seizures, and intraventricular conduction disturbances, and treatment options include good supportive care. We report two cases of lamotrigine poisoning in which multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine. CASE 1: A 21-year-old woman ingested 15.6 g lamotrigine, 14 g levetiracetam, and 15 mg clonazepam. She became comatose and developed generalized tonic seizure. One hour post-ingestion, 50 g activated charcoal was administered. Starting 11 h post-ingestion, 25 g activated charcoal was administered every 4 h for 4 doses. The peak concentration of serum lamotrigine was 49.5 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 6.5 h. CASE 2: A 46-year-old woman ingested 0.3 g lamotrigine and 0.1 g topiramate twice, 2 h apart. She became drowsy, complained of blurred vision, vertigo, nausea, and vomited. An initial dose of 50 g activated charcoal was administered at 4.5 h post-second ingestion, and subsequent doses of 25 g (total of 3 doses) were administered every 4 h, commencing at 8.5 h post-second ingestion. The peak concentration of serum lamotrigine was 19.9 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 9.3 h. DISCUSSION: The mean elimination half-life of lamotrigine in healthy volunteers and epileptic patients receiving lamotrigine monotherapy is 22.8-37.4 h. In our two cases, multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine, possibly by inhibiting enterohepatic circulation. Multiple-dose activated charcoal should be considered an option for treating lamotrigine poisoning.

Investigation of site and frequency of asymptomatic injury in medial structures of the elbow in adolescent baseball players using dedicated magnetic resonance imaging.

PURPOSE: Medial epicondyle (ME) and elbow joint proximal (UCL-p) and distal ulnar collateral ligament (UCL-d) asymptomatic injuries are frequently observed using magnetic resonance imaging (MRI). However, the injury rates vary among these structures in elbow screening of adolescent baseball players, despite being adjacent medial structures of the elbow. This study aimed to retrospectively determine the actual injury site and rate, and investigate the underlying reason for discrepancies anatomically and biomechanically. MATERIALS AND METHODS: Forty-four male adolescent baseball players were scanned using MRI. Two interpreters independently and retrospectively assessed the ME, UCL-p, and UCL-d injuries using the gradient echo axial, sagittal, and coronal planes. RESULTS: The injury prevalence was significantly higher in the ME and UCL-p (> 50% of the participants) than in the UCL-d (22.7%), P < 0.01 and P < 0.01, respectively. Additionally, there was a tendency toward a high-frequency injury rate of the ME or UCL-p. CONCLUSION: The injury site of the medial structures tended to be proximal. The ME and UCL-p were observed to be more frequently injured compared to the UCL-d in adolescent baseball players according to the dedicated MRI findings in this study.

Isolated Distal Fibular Stress Fracture after Total Hip Arthroplasty in a Patient with Developmental Dysplasia of the Hip.

Stress fractures following total hip arthroplasty in the lower limbs away from the surgical area are very rare. We report a case of stress fracture in the isolated distal fibula that presented five months after total hip arthroplasty in a patient with developmental dysplasia of the hip. A 67-year-old woman diagnosed with coxarthrosis of the right hip joint, classified as Crowe's group 3, underwent total hip arthroplasty with acetabular reconstruction using a bulk bone graft. The surgery successfully treated the preoperative leg length discrepancy and flexion and external rotation contractures. The alignment of the right lower limbs changed from slight varus to valgus knee following surgery. The postoperative process went well; however, she experienced lateral ankle pain on the affected side five months after surgery. No obvious fracture was observed via radiograph; however, she received a subsequent diagnosis of isolated distal fibula stress fracture. Additionally, she was diagnosed with vitamin D deficiency. Valgus alignment change of the knee joint and vitamin D deficiency were considered the main causes of the stress fracture. Stress fractures should be suspected in patients complaining of unexpected pain following total hip arthroplasty, even in distant areas of the affected limb, especially in osteoporotic patients.

Ten-year results of 55 dysplasia hips of hip offset and leg length reconstruction in total hip arthroplasty with cementless tapered stems having a high offset option designed for dysplastic femur.

PURPOSE: In developmental dysplasia of the hip (DDH), the centers of hip rotation move in the superior and lateral direction. In total hip arthroplasty for such cases, movement of the center of hip rotation is in the inferior and medial direction. It causes an increase in leg length and a decrease in acetabular offset. We therefore evaluated the change of hip offset and leg length before and after surgery with two stems having a high offset option. PATIENTS AND METHODS: The preoperative diagnosis was secondary osteoarthritis due to DDH excluded Crowe IV. A stem selection was decided based on preoperative two-dimensional templating. Total 55 hips in 50 patients were followed up for minimum 10 years. Pre- and postoperative clinical evaluations were performed using a hip joint function scoring system. Radiographic evaluations were used for offset and leg length measurements and other associated factors. RESULTS: Both stems showed excellent clinical results. A high offset option was used in 60% of all cases. No postoperative dislocations were observed. The biological fixation was stable in all cases. The hip offset was restored without excessive leg lengthening in most cases. CONCLUSION: Anatomical consistency could be maintained by using a stem which matched geometry of the proximal part and had offset option. These cementless tapered stems having a high offset option are suitable for Crowe I to III hip dysplasia if two-dimensional X-ray templates fit the shape of the proximal femurs. They were associated with excellent clinical results and biological fixation. The offset option may be useful to adjust leg length and offset in DDH patients.

Surgical results of atypical femoral fractures in long-term bisphosphonate and glucocorticoid users - Relationship between fracture reduction and bone union.

Atypical femoral fracture (AFF) associated with bisphosphonate (BP) use is common, and its pathophysiology is considered to involve severely suppressed bone turnover. Surgical results following AFF fixation have not been optimal, with some cases resulting in delayed union or nonunion. Regarding bone healing, glucocorticoid (GC) has similar properties to BP. We investigated the surgical results of AFF fixation in both users of BP and GC, especially with regard to intraoperative fracture reduction. We included 12 AFFs in 11 patients with a follow-up over one year who all took GC for autoimmune disease and BP for management of GC-induced osteoporosis. Their mean age was 62 years and 10 patients were female. Six fractures were located in the subtrochanteric region of the femur and six were in the diaphysis. Intramedullary nails were used to treat all fractures. Union rate was recorded, and the status of the reduction immediately after the operation was analyzed. Four of the 12 cases developed nonunion, and three of them required additional surgery. The relationship between alignment, cortical continuity, fracture gap, and bone union was not significant. In the nonunion cases, cortical continuity on the anteroposterior and lateral views were never confirmed. Even if cortical continuity in either of the views was there, the two limbs resulted in nonunion. One third of the patients with AFF secondary to long-term BP and GC use developed nonunion despite their fracture reductions being acceptable. We consider strict reduction should be needed for these cases with disadvantage condition to bone union.

An ultra-rapid drug screening method for acetaminophen in blood serum based on probe electrospray ionization-tandem mass spectrometry.

Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 µL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x2) was linear over the range of 1.56-200 µg/mL (r2 = 0.998), and the limit of detection and quantitation were 0.37 µg/mL and 1.56 µg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (-0.15-2.8% and 2.3-6.1%, respectively) and matrix effect at 3 concentrations (95.1-104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.

Application of probe electrospray ionization-tandem mass spectrometry to ultra-rapid determination of glufosinate and glyphosate in human serum.

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.

Change in MRI findings of medial collateral ligament injury in adolescent baseball players with no clinical symptoms over time.

OBJECTIVE: Elbow screening of adolescent baseball players began in 2014 using ultrasound, palpation, and dedicated magnetic resonance imaging (MRI). We frequently encountered subjects showing MCL injury on MRI but no clinical symptoms. We assessed variations in asymptomatic MCL injury findings at follow-up MRI, and clarified the pathogenesis of these findings. MATERIALS AND METHODS: Using a 0.2-T-dedicated MRI, 30 subjects with asymptomatic MCL injury at initial MRI who agreed to follow-up MRI were included. We classified the findings at repeat MRI as follows: (a) disappeared, (b) better, and (c) worse. RESULTS: There were 6, 16, and 8 subjects in groups a, b, and c, respectively. The average age at follow-up was 14.0, 12.1, and 12.4 years in groups a, b, and c, respectively. There were significant differences between groups a and b and between groups a and c. Average height at follow-up of groups a, b, and c was 1.64, 1.52, and 1.57 cm, respectively, with a statistically significant difference between groups a and b. The average size of the short axis of the MCL of subjects in group a was 2.0 cm on the dominant side and 1.5 cm on the contradominant side (P < 0.04). CONCLUSION: Players with asymptomatic MCL injury can continue to play baseball with no limitations, as these findings usually disappear around the age of 14.0 years, when the growth spurt occurs. This finding may be a precursor of 'adaptation', which is generally observed in high school baseball players, suggesting that the MCL adapts as growth occurs.

Cost-effectiveness analysis of drugs for osteoporosis treatment in elderly Japanese women at high risk of fragility fractures: comparison of denosumab and weekly alendronate.

This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment. Denosumab treatment was cost-effective compared with alendronate treatment for elderly Japanese women at high risk of fragility fractures. Denosumab treatment might be cost-effective for patients with lower bone mineral density. PURPOSE: In Japan's super-aged society, the prevention and treatment of osteoporosis are a critical issue with implications for the medical economy. This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment with denosumab versus weekly alendronate for elderly Japanese women at high risk of fragility fractures. METHODS: A Markov model was used for simulation analysis. The modeled population was 75-year-old Japanese women with a bone mineral density (BMD) of 65% of the young adult mean (YAM) (T-score, - 2.87) and a history of previous vertebral body fracture. The simulation model was repeated until patient age reached 100 years or death. Analysis was performed from the societal perspective. Costs and epidemiological data were derived from previous studies. The incremental cost-effectiveness ratio (ICER) was calculated from the simulation. We compared the ICER with willingness-to-pay. Additional analyses were performed with different combinations of age and BMD. Sensitivity analysis verified the robustness of the analysis. RESULTS: For the modeled population, the ICER of denosumab versus alendronate treatment was estimated at US$40,241/quality-adjusted life year (QALY). The ICER of denosumab for 80-year-old women whose BMD was 60% of YAM was estimated at US$22,469/QALY. CONCLUSIONS: Assuming willingness-to-pay as US$50,000/QALY, denosumab treatment for 75-year-old Japanese women with a BMD of 65% of YAM and a history of previous vertebral body fracture was cost-effective compared with alendronate treatment. Among over 75 years of age, denosumab treatment might be more cost-effective than alendronate for patients with a BMD of 65% of YAM or lower.

Mild manifestation of methanol poisoning half a day after massive ingestion of a fuel alcohol product containing 70% ethanol and 30% methanol: a case report.

CASE: Is fomepizole necessary after massive ingestion of a mixture of methanol and ethanol? We report the case of a 37-year-old man who was transported to our Poison Center 12 h after ingesting 500 mL of fuel alcohol containing 70% methanol and 30% ethanol in a suicide attempt. On admission, he presented only with somnolence and mild metabolic acidosis. We hypothesized that most of the ethanol had been metabolized. OUTCOME: As the estimated serum concentration of methanol was lethal (242.6 mg/dL), fomepizole was given i.v. and hemodialysis was carried out twice, resulting in complete recovery. Later, the serum concentrations of both methanol and ethanol on admission were found to be 224.1 and 0.51 mg/dL, respectively. CONCLUSION: Therapeutic intervention was delayed by half a day after ingestion of a product containing methanol and ethanol in the present case. If the patient had arrived earlier, he may have only been treated with hemodialysis, but not fomepizole.