Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2)

Context: Paracetamol is commonly taken in overdose, with increasing concerns that those taking “massive” overdoses have higher rates of hepatotoxicity and may require higher doses of acetylcysteine. The objective was to describe the clinical characteristics and outcomes of “massive” (≥?40?g) paracetamol overdoses.

Methods: Patients were identified through the Australian Paracetamol Project, a prospective observational study through Poisons Information Centres in NSW and Queensland, over 3 and 1.5 years, respectively, and retrospectively from three clinical toxicology unit databases (over 2.5 to 20 years). Included were immediate-release paracetamol overdoses ≥?40?g ingested over ≤?8?h. Outcomes measured included paracetamol ratio[defined as the ratio of the first paracetamol concentration taken 4–16?h post-ingestion to the standard (150?mg/L at 4?h) nomogram line at that time] and hepatotoxicity (ALT >1000?U/L).

Results: Two hundred paracetamol overdoses were analysed, reported median dose ingested was 50?g (interquartile range (IQR): 45–60?g) and median paracetamol ratio 1.9 (IQR: 1.4–2.9, n?=?173). One hundred and ninety-three received acetylcysteine at median time of 6.3?h (IQR: 4–9.3?h) post-ingestion. Twenty-eight (14%) developed hepatotoxicity, including six treated within 8?h of ingestion. Activated charcoal was administered to 49(25%), at median of 2?h post-ingestion (IQR:1.5-5?h). Those receiving activated charcoal (within 4?h of ingestion), had significantly lower paracetamol ratio versus those who did not: 1.4 (n?=?33, IQR: 1.1–1.6) versus 2.2 (n?=?140, IQR: 1.5–3.0) (p?Seventy-nine had a paracetamol ratio ≥2, 43 received an increased dose of acetylcysteine in the first 21?h; most commonly a double dose in the last bag (100 to 200?mg/kg/16?h). Those receiving increased acetylcysteine had a significant decrease risk of hepatotoxicity [OR:0.27 (95% CI: 0.08–0.94)]. The OR remained similar after adjustment for time to acetylcysteine and paracetamol ratio.

Conclusion: Massive paracetamol overdose can result in hepatotoxicity despite early treatment. Paracetamol concentrations were markedly reduced in those receiving activated charcoal within 4?h. In those with high paracetamol concentrations, treatment with increased acetylcysteine dose within 21?h was associated with a significant reduction in hepatotoxicity.     

CT fluoroscopy-guided percutaneous drainage: comparison of the one step and the Seldinger techniques

Objective: To evaluate the one step technique compared with the Seldinger technique in computed tomography (CT) fluoroscopy-guided percutaneous drainage of abdominal and pelvic abscess.

Material and methods: Seventy-six consecutive patients (49 men, 27 women; mean age 63.5 years, range 19–87 years) with abdominal and pelvic abscess were included in this study. Drainages were performed with the one step (n?=?46) and with the Seldinger (n?=?48) technique between September 2012 and June 2014.

Results: The technical success and clinical success rates were 95.8% and 93.5%, respectively, for the one step group, and 97.8% and 95.7%, respectively, for the Seldinger group. The mean procedure time was significantly shorter with the one step than with the Seldinger method (15.0?±?4.3?min, range 10–29?min vs. 21.0?±?9.5?min, range 13–54?min, p?Conclusion: The one step technique was easier and faster than the Seldinger technique. The effectiveness of both techniques was similar for the CT fluoroscopy-guided percutaneous drainage of abdominal and pelvic abscess.     

Laparoscopic near-total splenectomy: a single-center experience of a standardized procedure

Abstract

Background: Near-total splenectomy (NTS) represents an innovative and effective surgery technique for spleen disease, reducing the risk of severe infections and thromboembolic events after total splenectomy. The authors reported a laparoscopic near-total splenectomy (LNTS) surgical experience following the optimal results of the open approach, describing a standardized and effective minimally invasive technique with the purpose of preserving a minimal residual spleen.

Material and methods: From November 2006 to September 2016, 15 patients with splenic and hematologic disease underwent LNTS, according to a laparoscopic procedure developed by the authors. The end criterion was to conserve a remanent spleen of 10–15?cm³ in size.

Results: Patient age ranged between 18 and 59 years. Mean operative time was 70?±?20?min. Mean hospital stay was 3.46 (range 3–7) days. One complication occurred during the surgery for a lesion of the inferior polar artery with need of a total splenectomy. No conversion to open surgery was necessary.

Conclusions: LNTS is a safe and effective technique for the management of splenic and hematologic disease with a low intra- and post-operative complication rate, and it can minimize the late sequelae of secondary splenectomy. However, it requires further studies with more cases to evaluate its role.     

The use of sustained low efficiency dialysis (SLED) in massive paracetamol overdose

Context: Massive paracetamol ingestion causing mitochondrial dysfunction is uncommon. Use of sustained low-efficiency dialysis (SLED) to improve acidaemia and enhance paracetamol elimination has not been previously described.

Case details: A 44-year-old male presented to the emergency department 2.5?hours post overdose of 200?g (2.5?g/kg) of paracetamol. Examination revealed a BP 85/60?mmHg, pulse 112 bpm, temperature 33.9?°C and blood glucose of 13.9?mmol/l. Venous blood gas 5.5-hours post-ingestion showed a pH 6.9, pCO₂ 58?mmHg, HCO₃ 13?mmol/l and lactate 14?mmol/l. Fifty-grams of nasogastric activated charcoal and double-strength intravenous acetylcysteine were administered. Paracetamol concentration peaked at 4207 µmol/l six hours post-ingestion. SLED was commenced nine-hours post ingestion and acetylcysteine dose was doubled again during dialysis. Paracetamol extraction ratio was 47–52%. Plasma paracetamol clearance was steady throughout SLED (53–58?ml/min). Hepatotoxicity did not develop and the patient recovered.

Discussions: Intermittent hemodialysis (IHD) is more efficient than SLED or continuous renal replacement therapy for enhancing paracetamol elimination and clearance. IHD plasma clearance is reported to range from 36 to 215?ml/min compared with endogenous clearance of 224?ml/70?kg/min.

Conclusions: SLED improved acidaemia with only moderate overall increase in paracetamol plasma clearance. Lack of development of hepatotoxicity was likely the result of early administration of acetylcysteine rather than any effect of SLED on paracetamol elimination.     

Validation of the Stroke and Aphasia Quality of Life Scale in a multicultural population

Purpose: This study aimed to determine the reliability and validity of the Stroke and Aphasia Quality of Life Scale (SAQOL-39?g) and its Mandarin adaptation SAQOL-CSg in Singaporean stroke patients.

Method: First-time stroke survivors were recruited at three months post-stroke and underwent a series of questionnaires in their dominant language (English/Mandarin). This included: SAQOL-39?g/CSg, National University Hospital System (NUHS) Aphasia Screening Test, Barthel Index, Modified Rankin Scale, Mini Mental State Examination, Frontal Assessment Battery, Center for Epidemiologic Studies Depression Scale and the Eurol-Qol Health Questionnaire (EQ-5D). The SAQOL-39?g/SAQOL-CSg was repeated within 1 week (±?6 days).

Results: Ninety-four participants (96.9%) were able to self-report and their results presented here. Both the SAQOL-39?g/SAQOL-CSg showed good internal consistency (α?=?0.96/0.97), test–retest reliability (ICC=?0.99/0.98), convergent (r_s ?=0.64–0.81 and 0.66–0.88, respectively) and discriminant (r_s?=?0.35–0.53 and 0.48–0.62, respectively) validity. The correlation between the SAQOL-39?g and the EQ-5D Visual Analogue Scale was 0.27. Further inspection of the EQ-5DVAS scores revealed correlations in different directions for Malay versus Chinese participants.

Conclusions: Both the SAQOL-39?g and SAQOL-CSg demonstrated good reliability and validity. Our results suggested some influence of ethnicity in self-rating of health status in relation to SAQOL-39?g scores. Further research is warranted to examine its use with stroke survivors with greater stroke severity and over time.

• Implications for Rehabilitation

• Validation of SAQOL in Singapore:

• Both the SAQOL-39g and the SAQOL-CSg may be used to measure the HRQoL of stroke survivors with and without aphasia in Singapore.

• Further investigation is required to examine use with stroke survivors with greater stroke severity and over time.

     

What can clinicians learn from therapeutic studies about the treatment of acute oral methotrexate poisoning?

Context: Methotrexate (MTX) is an anti-folate drug that has been utilized in both malignant and chronic inflammatory conditions. Doctors are often concerned with a potential adverse outcome when managing patients with acute oral MTX poisoning given its potential for serious adverse reactions at therapeutic doses. However, there is surprisingly little data from acute poisoning cases and more data from the therapeutic use of high-dose MTX.

Objectives: To review pharmacokinetic and pharmacological properties of MTX and systematically review series of acute MTX poisonings and therapeutic studies on high-dose MTX that provide pharmacokinetic or clinical data.

Methods: An Embase (1974–October 2016) and Medline (1946–October 2016) search was performed by combining “MTX” and “overdose/poison” or “MTX” and “toxicity” or “MTX” and “high-dose MTX” or “MTX” and “bioavailability” or “pharmacokinetics”; 25, 135, 109 and 365 articles were found, respectively, after duplicates were removed. There were 15 papers that provided clinical data on acute ingestion and toxicity that occurred with low-dose administration. Eighteen papers were on high-dose MTX (>1?g per m² body surface area) used as a single chemotherapy agent which provided pharmacokinetic or clinical data on MTX toxicity. Thirty papers were reviewed to determine the toxic dose, pharmacokinetics, risk factors, clinical symptoms and management of acute MTX toxicity. Given the limited acute poisoning data, a retrospective audit was performed through the consultant records of the New South Wales Poisons Information Centre from April 2004 to July 2015 to examine the clinical syndrome and toxicity of acute oral MTX poisoning.

Pharmacokinetics: Reduced MTX bioavailability is a result of saturable absorption. Although maximal bioavailable absorption occurs at a dose of ～15?mg?m^?2, splitting the dose increases bioavailability. MTX clearance is proportional to renal function.

Acute toxicity: Oncologists prescribe doses up to 12?g?m^?2 of MTX. Patients treated with an intravenous dose of MTX?<1g?m^?2 do not require folinic acid rescue. MTX toxicity correlates better with duration and extent of exposure than peak serum concentration.

Acute oral poisoning: Acute oral MTX poisoning in 177 patients did not report any severe toxicity. In the New South Wales Poisons Information Centre audit data (2004–2015), 51 cases of acute MTX poisoning were reported, of which 15 were accidental paediatric ingestions. The median reported paediatric ingestion was 50?mg (IQR: 10–100; range: 10–150) with a median age of 2 years (IQR: 2–2; range: 1–4). Of the 36 patients with acute deliberate MTX poisoning, median age and dose were 47 years (IQR: 31–62; range: 10–85) and 325?mg (IQR: 85–500; range: 40–1000), respectively. Of the 19 patients who had serum MTX concentrations measured, all were significantly below the concentrations used in oncology and the folinic acid rescue nomogram line and no patient reported adverse sequelae.

Management of acute oral poisoning: Due to the low bioavailability of MTX, treatment is not necessary for single ingestions. Oral folinic acid may be used to lower the bioavailability further with large ingestions?>1?g?m^?2. Oral followed by intravenous folinic acid may be used in patients with staggered ingestion?>36?h or patients with acute overdose and renal impairment (eGFR <45?mL/min/1.73?m²).

Conclusions: As a consequence of saturable absorption MTXs bioavailability is so low that neither accidental paediatric MTX ingestion nor acute deliberate MTX overdose causes toxicity. An acute oral overdose will not provide a bioavailable dose even close to 1?g?m^?2 of parenteral MTX. Hence, no treatment is required in acute ingestion unless the patient has renal failure or staggered ingestion. There is also no need to monitor MTX concentrations in acute oral MTX poisoning.     

Acupuncture treatments for infantile colic: a systematic review and individual patient data meta-analysis of blinding test validated randomised controlled trials

Objective: Needle acupuncture in small children has gained some acceptance in Western medicine. It is controversial, as infants and toddlers are unable to consent to treatment. We aimed to assess its efficacy for treating infantile colic.

Design: A systematic review and a blinding-test validation based on individual patient data from randomised controlled trials. Primary end-points were crying time at mid-treatment, at the end of treatment and at a 1-month follow-up. A 30-min mean difference (MD) in crying time between acupuncture and control was predefined as a clinically important difference. Pearson’s chi-squared test and the James and Bang indices were used to test the success of blinding of the outcome assessors [parents].

Eligibility criteria and data sources: We included randomised controlled trials of acupuncture treatments of infantile colic. Systematic searches were conducted in Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, and in the Chinese language databases CNKI, VIP, Wang fang, SinoMed and Chinese Clinical Trial Registry.

Results: We included three randomised controlled trials with data from 307 participants. Only one of the included trials obtained a successful blinding of the outcome assessors in both the acupuncture and control groups. The MD in crying time between acupuncture intervention and no acupuncture control was ?24.9?min [95% confidence interval, CI ?46.2 to ?3.6; three trials] at mid-treatment, ?11.4?min [95% CI ?31.8 to 9.0; three trials] at the end of treatment and ?11.8?min [95% CI ?62.9 to 39.2; one trial] at the 4-week follow-up. The corresponding standardised mean differences [SMDs] were ?0.23 [95% CI ?0.42 to ?0.06], ?0.10 [95% CI ?0.29 to 0.08] and ?0.09 [95% CI ?0.48 to 0.30]. The heterogeneity was negligible in all analyses. The statistically significant result at mid-treatment was lost when excluding the apparently unblinded study in a sensitivity analysis: MD ?13.8?min [95%CI ?37.5 to 9.9] and SMD ?0.13 [95%CI ?0.35 to 0.09]. The registration of crying during treatment suggested more crying during acupuncture [odds ratio 7.7; 95% CI 2.7–20.6; one trial]. GRADE-Moderate quality evidence.

Conclusions: Percutaneous needle acupuncture treatments should not be recommended for infantile colic on a general basis.

Systematic review registration: PROSPERO 2015:CRD42015023253

• Key points

• The role of acupuncture in the treatment of infantile colic is controversial. Available trials are small and present conflicting results.

• There were no clinically important differences between infants receiving acupuncture and no acupuncture control in this IPD meta-analysis of randomised controlled trials.

• The data indicate that acupuncture induces some treatment pain in many of the children.

• The study results indicate that percutaneous needle acupuncture should not be recommended for treatment of infantile colic on a general basis.

     

Zero-order metoprolol pharmacokinetics after therapeutic doses: severe toxicity and cardiogenic shock

Objective: Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment.

Case details: A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250?mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10?U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76?L/min/m²). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX^® vs 4.3 (www.lixoft.com). Admission metoprolol concentration was 2.39?μg/mL (therapeutic reference range: 0.035–0.5?μg/mL). Data best fitted a one compartmental model with Michaelis–Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4?L, maximum rate [V_m], 9.57?mg?h^?1, Michaelis constant [K_m], 1.97?mg L^?1. Predicted elimination half-life decreased from 20?h over time until there was first order elimination with a half-life 9?h.

Conclusion: The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes.     

Feedback-controlled robotics-assisted treadmill exercise to assess and influence aerobic capacity early after stroke: a proof-of-concept study

Abstract

Purpose: The majority of post-stroke individuals suffer from low exercise capacity as a secondary reaction to immobility. The aim of this study was to prove the concept of feedback-controlled robotics-assisted treadmill exercise (RATE) to assess aerobic capacity and guide cardiovascular exercise in severely impaired individuals early after stroke. Method: Subjects underwent constant load and incremental exercise testing using a human-in-the-loop feedback system within a robotics-assisted exoskeleton (Lokomat, Hocoma AG, CH). Inclusion criteria were: stroke onset ≤8 weeks, stable medical condition, non-ambulatory status, moderate motor control of the lower limbs and appropriate cognitive function. Outcome measures included oxygen uptake kinetics, peak oxygen uptake (VO₂peak), gas exchange threshold (GET), peak heart rate (HRpeak), peak work rate (Ppeak) and accuracy of reaching target work rate (P-RMSE). Results: Three subjects (18–42?d post-stroke) were included. Oxygen uptake kinetics during constant load ranged from 42.0 to 60.2?s. Incremental exercise testing showed: VO₂peak range 19.7–28.8?ml/min/kg, GET range 11.6–12.7?ml/min/kg, and HRpeak range 115–161?bpm. Ppeak range was 55.2–110.9?W and P-RMSE range was 3.8–7.5?W. Conclusions: The concept of feedback-controlled RATE for assessment of aerobic capacity and guidance of cardiovascular exercise is feasible. Further research is warranted to validate the method on a larger scale.

• Implications for Rehabilitation

• Aerobic capacity is seriously reduced in post-stroke individuals as a secondary reaction to immobility.

• Robotics-assisted walking devices may have substantial clinical relevance regarding assessment and improvement of aerobic capacity early after stroke.

• Feedback-controlled robotics-assisted treadmill exercise represents a new concept for cardiovascular assessment and intervention protocols for severely impaired individuals.

     

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning

Context: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined.

Objective: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning.

Methods: The study was designed as observational cohort study. The mean time for an increase of 1?mmol/L HCO₃^–, 0.01 unit arterial blood pH, and the total time for correction of HCO₃^– were determined in IHD- and CRRT-treated patients.

Results: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79?±?0.10 versus 7.05?±?0.10; p?=?0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO₃^– correction correlated with arterial blood pH (r=??0.511; p?=?0.003) and creatinine (r?=?0.415; p?=?0.020). There was association between the time to HCO₃^– correction and dialysate/effluent and blood flow rates (r=??0.738; p?r=??0.602; p?The mean time for HCO₃^– to increase by 1?mmol/L was 12?±?2?min for IHD versus 34?±?8?min for CRRT (p?p?=?0.024). The mean increase in HCO₃^– was 5.67?±?0.90?mmol/L/h for IHD versus 2.17?±?0.74?mmol/L/h for CRRT (p?Conclusions: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.     

Revisiting the physiological effects of methylene blue as a treatment of cyanide intoxication

Background: Although methylene blue (MB) had long been proposed to counteract the effects of cyanide (CN) intoxication, research on its mechanisms of action and efficacy has been abandoned for decades. Recent studies on the benefits of MB in post-anoxic injuries have prompted us to reexamine the relevance of this historical observation.

Methods: Our study was performed in adult male Sprague–Dawley rats and on HEK293T epithelial cells. First, the effects and toxicity of MB (0–80?mg/kg) on circulation and metabolism were established in four urethane-anesthetized rats. Then nine rats received a lethal infusion of a solution of KCN (0.75?mg/kg/min) and were treated by either saline or MB, at 20?mg/kg, a dose that we found to be innocuous in rat and to correspond to a dose of about 4?mg/kg in humans. MB was also administered 5?min after the end of a sub-lethal exposure to CN in a separate group of 10 rats. In addition, ATP/ADP ratio, ROS production, mitochondrial membrane potential (Δψm) and cellular O₂ consumption rate (OCR) were determined in HEK293T cells exposed to toxic levels of CN (200?µM for 10?min) before and after applying a solution containing MB (1–100?µM for 10?min).

Results: Methylene blue was found to be innocuous up to 50?mg/kg. KCN infusion (0.75?mg/kg/min) killed all animals within 7–8?min. MB (20?mg/kg) administered at the same time restored blood pressure, cardiac contractility and limited O₂ deficit, allowing all the animals to survive, without any significant methemoglobinemia. When administered 5?min after a non-lethal CN intoxication, MB sped up the recovery of lactate and O₂ deficit. Finally, MB was able to decrease the production of ROS and restore the ATP/ADP ratio, Δψm as well as OCR of epithelial cells intoxicated by CN.

Conclusions: The present observations should make us consider the potential interest of MB in the treatment of CN intoxication. The mechanisms of the antidotal properties of MB cannot be accounted for by the creation of a cyanomethemoglobinemia, rather its protective effects appears to be related to the unique properties of this redox dye, which, depending on the dose, could directly oppose some of the consequences of the metabolic depression produced by CN at the cellular level.     

The effect of different flow levels and concentrations of sevoflurane during the wash-in phase on volatile agent consumption: a randomized controlled trial

Purpose

The standard procedure for low-flow anesthesia usually incorporates a high fresh gas flow (FGF) of 4–6 L/minute during the wash-in phase. However, the administration of a high FGF (4–6 L/min) increases the inhaled anesthetic agent consumption. This study was designed to compare the sevoflurane consumption at 2 rates of flow and vaporizer concentration during the wash-in period.

Methods

Patients were randomly enrolled into high FGF (HFGF) (n?=?30) and low FGF (LFGF) (n?=?30) groups. During the wash-in, the HFGF group received 4 L/minute FGF with a sevoflurane vaporizer setting of 2.5%, and the LFGF group received 1 L/minute FGF with a vaporizer setting of 8%. Once the wash-in was complete, anesthesia maintenance was performed with 0.5 L/min FGF with a vaporizer setting of 2.5–4.5% in both groups. The patient demographic data, bispectral index values, hemodynamic variables, wash-in time, sevoflurane consumption during the wash-in phase, and total sevoflurane consumption were analyzed.

Results

The median sevoflurane consumption in the wash-in phase was 8.2 mL (7.1–9.3) in the HFGF group and 2.7 mL (2.2–3.1) in the LFGF group (p?=?0.001). The mean total sevoflurane consumption was 17.41?±?3.58 mL in the patients who received HFGF and 14.93?±?3.57 mL in the LFGF group (p?=?0.001). The mean wash-in completion time was 12.49?±?2.79 min in the HFGF group and 3.35?±?0.67 min in the LFGF group (p?=?0.001).

Conclusions

The anesthetic agent consumption during the wash-in phase was approximately 3 times lower with the administration of sevoflurane at 1 L/minute FGF than the use of 4 L/minute FGF.

     

Modified release paracetamol overdose: a prospective observational study (ATOM-3)

Background: Modified-release (MR) paracetamol is available in many countries as 665?mg tablets of which 69% is MR and 31% is immediate release. There are concerns that MR paracetamol overdose has higher rates of liver injury despite standard treatment algorithms. The objective of this study was to describe the clinical characteristics and outcomes of acute MR paracetamol overdose.

Methods: Prospective observational study, recruiting patients from January 2013 to June 2017, from five clinical toxicology units and calls to two Poisons Information Centres in Australia. Included were patients >14 years who ingested ≥10?g or 200?mg/kg (whichever is less) of MR paracetamol. Data collected included demographics, ingestion history, pathology results, treatments, and outcomes including hepatotoxicity (ALT >1000?U/L).

Results: In total, 116 patients were recruited, 85(73%) were female. The median dose ingested was 32?g (IQR: 20–49?g) and median time to presentation was 3?h (IQR: 2–9?h). 78(67%) had an initial paracetamol concentration above the nomogram line (150?mg/L at 4?h). A further 12(10%) crossed the nomogram after repeat paracetamol measurements, of which five crossed after two non-toxic levels 4?h apart. Six had a double paracetamol peak, in three occurring >24?h post-ingestion. 113(97%) received acetylcysteine of which 67 received prolonged treatment beyond the standard 21?h. This was because of an elevated paracetamol concentration at the completion of acetylcysteine in 39 (median paracetamol concentration 25?mg/L, IQR: 16–62?mg/L). 21 (18%) developed hepatotoxicity, including six treated within 8?h of ingestion. Activated charcoal and double doses of acetylcysteine did not significantly decrease the risk of hepatotoxicity.

Conclusions: Drug regulatory authorities are considering restrictions on MR paracetamol preparations. Following an acute MR paracetamol overdose, this study found that many patients had a persistently elevated paracetamol concentrations, many required prolonged treatment and some developed liver injury despite early acetylcysteine treatment. Furthermore, activated charcoal and increased acetylcysteine did not appear to significantly alter the risk of liver injury. Hence, research into better treatment strategies is required.

Trial registration: Australian Toxicology Monitoring (ATOM) Study – Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.     

Management of severe pain after dermal contact with caterpillars (erucism): a prospective case series

Context: Erucism, envenomation caused by dermal contact with larval forms of moths, may result in intense local pain, mainly after contact with puss caterpillars (family Megalopygidae).

Objective: To evaluate the response to different treatments for controlling severe pain in a case series of erucism in Campinas, southeastern Brazil.

Patients and methods: Prospective cohort study. A Numeric Pain Rating Scale (NPRS 0–10) was used to assess pain intensity in the Emergency Department (ED). Pain was considered as severe upon ED admission (T0) when the NPRS was ≥8. Inclusion criteria: age ≥8 years old, severe pain at T0, with continuous assessment of pain intensity in all patients using the NPRS during the ED stay (T5, T15, T30, T60?min and at discharge).

Results: Fifty-five patients fulfilled the inclusion criteria and were divided into three groups according to the initial treatment at T0: local anesthesia alone with 2% lidocaine (group 1, n?=?15), local anesthesia and analgesics (group 2, n?=?26) and analgesics without local anesthesia (group 3, n?=?14). Most patients were admitted within 2?h after dermal contact with the stinging bristles of caterpillars (median =90?min, IQR: 40–125?min). In 22 cases (40%), the caterpillar was brought for identification (Podalia spp., n?=?18; Megalopyge spp., n?=?4). There was a significant decrease in pain from T5 onwards with all of the treatments. When the short-term response (T5 and T15) was considered, analgesia was more effective in groups 1 and 2 compared to group 3 (p?n?=?25/55), mainly in group 1 (n?=?11/15). The median length of stay in the ED was 120?min (IQR: 80–173?min).

Conclusions: The association of local anesthesia with analgesics was apparently a good combination for the rapid management of severe pain in the ED.     

Adult clonidine overdose: prolonged bradycardia and central nervous system depression,but not severe toxicity

Context: There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults.

Methods: This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200?μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records.

Results: From 133 admissions for clonidine poisoning (1988–2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14–65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100?μg (interquartile range [IQR]: 400–15,000?μg). Median LOS was 21h (IQR: 14–35?h) and there were no deaths. Glasgow coma score [GCS] <15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS <9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48?bpm (IQR: 40–57?bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p?=?0.02). 82/108 (76%) had bradycardia, median onset 2.5?h post-ingestion (IQR: 1.7–5.5?h) and median duration 20?h (2.5–83?h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000–12,000?μg developed early hypertension. Median minimum systolic BP was 96?mmHg (IQR: 90–105?mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2?mg (IQR: 1.2–2.4?mg), but only one patient given naloxone was documented to respond with partial improvement in GCS.

Discussion: Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.     

Clinical characteristics of α-pyrrolidinovalerophenone (α-PVP) poisoning

Context: α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone that has been abused in recent years. The clinical presentation of acute α-PVP poisoning has not been well characterized.

Objective: To elucidate the clinical features of acute α-PVP poisoning.

Materials and methods: This retrospective case series included eight subjects that visited our hospital emergency department (ED) between March 2012 and November 2014 and had analytically confirmed blood α-PVP levels. Data related to subject demographics, clinical history, laboratory findings, blood drug levels, and outcome were collected.

Results: The median age of the eight study subjects was 27 (range; 21–63) years, and six were male. Drug preparations had been administered by rectal insertion (three subjects) or inhalation (five subjects). The time between drug exposure and presentation at the ED was 8.5 (1–24) h and blood α-PVP concentrations ranged from 1.0 to 52.5?ng/ml. Although psychiatric and neurological findings were reported before arrival at the ED in 5/8 and 7/8 subjects, respectively, these were only observed in 1/8 and 2/8 subjects, respectively, at the ED. Symptoms of high body temperature (3/8), tachycardia (5/8), hypertension (3/8), acid-base balance disorder (5/8), coagulopathy (4/6), blood creatinine phosphokinase?>190?U/l (6/8), and a blood lactate level?>?1.7?mmol/l (5/7) were observed. All subjects survived and were discharged.

Conclusions: This retrospective case series showed that after acute exposure to α-PVP, transient neuropsychiatric findings were accompanied by more persistent sympathomimetic physical findings, disorders of acid-base balance and blood coagulation, high blood creatinine phosphokinase, and hyperlactacidemia.     

Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose

Context: High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available.

Objective: To determine the stability of insulin at 16 units/mL in 0.9% saline solution.

Materials and methods: Eight-hundred units of regular insulin (8?mL from a stock vial containing 100 units/mL) were added to 42?mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4?°C (refrigerated) and two at 25?°C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days.

Results: Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days.

Discussion: Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid.

Conclusion: Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.     

Effects of kinesiologic taping on epidermal–dermal distance,pain, edema and inflammation after experimentally induced soft tissue trauma

Abstract

Purpose: In sports medicine, the use of kinesiologic tape has recently gained popularity. Although widely used, there is no study examining the effects of kinesiologic tape on soft tissue after a contusion injury. The aim of this study was to examine the effects of kinesiologic taping on epidermal–dermal distance, edema, pain and inflammation after experimentally induced contusion injury. Methods: Twelve adult female Wistar albino rats were divided into two groups: (1) 30?min group: n?=?6, weight range: 182.0–199.4?g; and (2) 6?h group: n?=?6, weight range: 186.9–200.8?g. After soft-tissue trauma, tape was applied to the right sides of each rat. In one group, tape was applied for 30?min while 6?h in the other. To assess the epidermal–dermal distance and edematous area, tissue sections were stained with hematoxylin and eosin and examined. Tissue sections were stained with nerve growth factor (NGF) and B-cell lymphoma 2 (Bcl-2) immunohistochemically to evaluate the effect of taping on pain and inflammation respectively. Results: Epidermal–dermal distances were found to be significantly higher than controls’ in both groups (p?<?0.05). Notable decreases were seen in edematous areas in both groups (p?<?0.05). NGF and Bcl-2 immune reactivity were decreased in all tape applied sides. Conclusions: After soft-tissue trauma, it was histologically shown that kinesiologic taping increases epidermal–dermal distance, and may reduce the sensation of pain, edema and inflammation. For better, faster and comfortable tissue healing with protection of soft-tissue integrity, kinesiologic taping may be a valuable treatment after contusion injury. However, these results should be supported by clinical studies.