Circulatory collapse during wound closure in spine surgery with an unknown cause: a possible adverse effect of topical application of vancomycin?

BACKGROUND: Vancomycin (VCM) is effective in fighting Gram-positive bacteria related severe infections, and topical application of VCM powder is widely used in orthopedic surgery to prevent wound infection. However, VCM could lead to infusion rate-dependent antibody-and complement-independent anaphylaxis reaction by inducing direct release of histamine. CASE PRESENTATION: We retrospectively analyzed seven cases of severe hypotension and shock during wound closure or immediately after orthopedic surgery with unidentifiable reasons. We found that these cases were all associated with local application of VCM powder during wound closure process. Two patients experienced sudden cardiac arrest. Most of the cases (6/7) with circulatory collapse were discharged without severe sequelae. While one case with application of 3 g VCM developed cardiac arrest and remained in a coma due to hypoxic-hypoxic encephalopathy. The clinical presentations and the time of the shock onset were considered to be related with a VCM induced anaphylaxis reaction. However, as this was a retrospective study, and there was no laboratory examination performed, the conclusion was made upon differential diagnosis based on clinical manifestations and the timing of the shock. CONCLUSIONS: Local application of VCM may not be as safe as was once believed and may lead to a related anaphylaxis. As VCM induced infusion-rate dependent, non-IgE mediated anaphylaxis is characterized by delayed occurrence, severe hypotension and even circulatory collapse, surgeons and anesthesiologists should be extra vigilant during and after VCM application.

Theophylline toxicity: Successful management of a patient with distributive shock secondary to drug overdose.

Presenting a case of acute theophylline and salbutamol overdose with distributive shock. Twenty one years old lady presented with history of consumption of 3 gram of theophylline and 40 mg of salbutamol. On admission she had altered sensorium with the systolic blood pressure of 60 mmHg, unrecordable diastolic blood pressure and heart rate of 147/min. Investigations revealed severe metabolic acidosis, hypokalemia, hypocalcemia which was managed by intravenous fluids, vasopressors, infusion of injection calcium gluconate and injection potassium chloride. As her hemodynamic status did not improve, she has been initiated on 1.5 mL/kg of lipid emulsion as bolus and then 0.5 mL/kg/h as infusion. Her hemodynamic status improved gradually and she was discharged in 24 h. Lipid emulsion had been used in local anesthetics and many tablet overdoses. In this patient timely administration of lipid emulsion resulted in early recovery of shock.

[Severe Shock Symptoms Due to Ticagrelor Related Anaphylactoid Reaction Following ST Elevation Myocardial Infarction]. / Schwere Schocksymptomatik infolge anaphylaktoider Reaktion auf Ticagrelor.

BACKGROUND: Ticagrelor as a P2Y12 receptor antagonist is recommended in patients with acute coronary syndrome without a primary cardiosurgical therapy. Severe relevant side effects, especially anaphylactic reactions, have not yet been described in the current literature. CASE PRESENTATION: We describe the first documented case in the current literature with a severe anaphylaxis after ticagrelor in a 76-year-old male patient with ST-elevation myocardial infarction. The diagnosis seems to be objectivated by the observed time-related life-threatening event after repetitive administration of ticagrelor and the rapid stabilization after adequate anaphylactic treatment. CONCLUSION: This case should raise the awareness that a supposedly safe drug can still cause an anaphylactic shock.

A somnolent woman in her fifties with acute circulatory failure. / En somnolent kvinne i 50-årene med akutt sirkulasjonssvikt.

BACKGROUND: A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation. CASE PRESENTATION: On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6. INTERPRETATION: Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.

[Establishment of new evaluation standards for systemic anaphylactoid reactions using mouse model].

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock.

BACKGROUND: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process. METHODS: Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases. RESULTS: Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1ß were elevated. CONCLUSIONS: This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.

The role of Syk/IĸB-α/NF-ĸB pathway activation in the reversal effect of BAY 61-3606, a selective Syk inhibitor, on hypotension and inflammation in a rat model of zymosan-induced non-septic shock.

Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, plays an important role in allergic diseases and inflammation. Syk triggers several intracellular signalling cascades including Toll-like receptor signalling to activate inflammatory responses following fungal infection but the role of this enzyme in zymosan (ZYM)-induced non-septic shock and its impacts on hypotension and inflammation in rats is not well understood. This study was conducted to determine the effects of Syk inhibition on ZYM-induced alterations in the expression and/or activities of Syk, inhibitor ĸB (IĸB)-α, and nuclear factor-ĸB (NF-ĸB) p65. We also examined the effect of Syk inhibition on inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumour necrosis factor (TNF)-α, and activity of myeloperoxidase (MPO) that contribute to hypotension and inflammation. Administration of ZYM (500 mg/kg, ip) to male Wistar rats decreased blood pressure and increased heart rate. These changes were associated with increased expression and/or activities of Syk, NF-κB p65, iNOS and COX-2 and decreased expression of IκB-α with enhanced levels of nitrite, nitrotyrosine, 6-keto-PGF1α , and TNF-α and activity of MPO in renal, cardiac and vascular tissues. ZYM administration also elevated serum and tissue nitrite levels. The selective Syk inhibitor BAY 61-3606 (3 mg/kg, ip) given 1 hour after ZYM injection reversed all of these changes induced by ZYM. These results suggest that Syk/IĸB-α/NF-ĸB pathway activation contributes to hypotension and inflammation caused by the production of vasodilator and proinflammatory mediators in the zymosan-induced non-septic shock model.

Oral Dipyridamole-Associated Circulatory Collapse.

Extended-release dipyridamole plus aspirin is widely used for secondary prevention of ischemic stroke, although the molecular pharmacodynamics of dipyridamole are not completely determined. Adverse effects of fixed-dose combination of aspirin and dipyridamole include headache, bleeding, and gastrointestinal events. Previously, intravenous infusion of dipyridamole in cardiac stress testing has been associated with cardiogenic shock and pulmonary edema. Herein, we report a case study of a 72-year-old man, presented with a transient ischemic attack who suffered a circulatory collapse after an oral dose of 200 mg extended-release dipyridamole. The possible molecular mechanisms of dipyridamole on the cardiovascular system are reviewed. This is the first case report of a circulatory collapse induced by an oral intake of dipyridamole.

Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity.

OBJECTIVE: The aim of this report is to describe a case of atrial fibrillation and shock precipitated by deliberate self-poisoning with theophylline. CLINICAL PRESENTATION AND INTERVENTION: An 85-year-old male with severe theophylline intoxication in a suicide attempt was admitted with severe cardiac arrhythmia and shock; despite poor prognosis, he fully recovered gradually after proper diagnosis and treatment. Theophylline is a rather forgotten medication; thus, intoxication is not usually considered among the etiologies of potentially treatable cardiologic emergencies, especially when its use is intentionally concealed. CONCLUSION: This case highlights the importance of identifying a comprehensive medication history using all available sources of information as early as possible in an emergency department presentation.

Shock and lethality with anthrax edema toxin in rats are associated with reduced arterial responsiveness to phenylephrine and are reversed with adefovir.

Although edema toxin (ETx) and lethal toxin (LTx) contribute to Bacillus anthracis shock and lethality, the mechanisms underlying their cardiovascular effects are unclear. We have previously shown that ETx but not LTx inhibited phenylephrine-stimulated contraction of aortic rings prepared from healthy rats and that adefovir, a selective inhibitor of ETx cAMP production, blocked this effect. Here, we examined arterial function in rats that received 24-h ETx or LTx infusions. Compared with control rats, ETx reduced mean arterial pressure (MAP) and survival over 48 h (P ≤ 0.0003) and increased plasma cAMP at 4, 24, and 48 h (P < 0.0001) and nitric oxide (NO) at 24 and 48 h (P ≤ 0.01). Compared with control animals, at 24- and 48-h phenylephrine stimulation of aortic rings from ETx animals produced decreased maximal contractile force (MCF; P = 0.05 and 0.006) and in vivo phenylephrine infusion in ETx animals produced decreased proportional increases in MAP (P < 0.0001 and P = 0.05). In ETx-treated animals, compared with placebo-treated animals, adefovir treatment prevented all lethality (P = 0.01), increased MAP (P ≤ 0.0001), decreased plasma and aortic tissue cAMP at 24 and 48 h, respectively (P ≤ 0.03), and plasma NO at both times (P ≤ 0.004), and increased phenylephrine-stimulated increases in MCF in aortic rings and MAP in vivo at 48 h (P = 0.02). LTx decreased MAP and survival also, but it did not alter the response to phenylephrine of MCF in aortic rings prepared from LTx animals or of MAP in vivo. In conclusion, in rats, hypotension and lethality are associated with reduced arterial contractile function with ETx but not LTx and adefovir improves ETx-induced hypotension and lethality.NEW & NOTEWORTHY The most important aspects of the present study are the findings that 1) in vivo challenge with anthrax edema but not lethal toxin depresses arterial contractile function measured both ex vivo and in vivo and 2) adefovir inhibits the effects of edema toxin on arterial hypotension and improves survival with lethal dose of edema toxin challenge.

The possibility of the treatment for long-acting injectable antipsychotics induced severe side effects.

We present the case of a 47-year-old man with schizophrenia who developed acute and persistent circulatory failure after receiving injections of paliperidone palmitate. We measured blood concentrations of paliperidone and performed resection of hip tissues, where paliperidone palmitate was suspected to be present, in order to reduce the side effects. Unfortunately, the resection could not save the patient from prolonged and severe side effects and he died of multiple organ failure. We suggest that resection of the tissues suspected of containing paliperidone palmitate can help reduce its severe side effects. However, identifying the site of injection is essential.

[Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures]. / Hypersensibilité aux sels de platine et aux taxanes : intérêt des tests cutanés et des inductions de tolérance.

AIM: The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. PATIENTS AND METHODS: This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. RESULTS: Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. CONCLUSION: This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.

A Case of Sudden Shock during Caesarean Section in whi ch Amniotic Fluid Embolism is Suspected.

We report a case of sudden shock during caesarean section under combined spinal epidural anesthesia. The patient was a 29-year-old woman. During the operation vital signs had been almost stable until a female-baby was born. But after the delivery of the placenta, the patient developed an episode of coughing and dyspnea followed by unconsciousness and bradycardia. She was given adrenaline and intubated, appearing ventricular fibrillation on a EKG. Cardiopulmonary resuscitation was immediately started and sinus rhythm returned. Hypotension followed and a small dose of adrenaline was infused for three days. She made good progress and was discharged without significant sequela. Cardiopulmonary collapse type of amniotic fluid embolism (AFE) is doubtful in this case. The necessity of rapid and appropriate treatment for emergency obstetric cases was discussed.

The deubiquitinase activity of A20 is dispensable for NF-κB signaling.

A20 has been suggested to limit NF-κB activation by removing regulatory ubiquitin chains from ubiquitinated substrates. A20 is a ubiquitin-editing enzyme that removes K63-linked ubiquitin chains from adaptor proteins, such as RIP1, and then conjugates them to K48-linked polyubiquitin chains to trigger proteasomal degradation. To determine the role of the deubiquitinase function of A20 in downregulating NF-κB signaling, we have generated a knock-in mouse that lacks the deubiquitinase function of A20 (A20-OTU mice). These mice are normal and have no signs of inflammation, have normal proportions of B, T, dendritic, and myeloid cells, respond normally to LPS and TNF, and undergo normal NF-κB activation. Our results thus indicate that the deubiquitinase activity of A20 is dispensable for normal NF-κB signaling.

Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.

Outcomes of Propofol Sedation During Emergency Endoscopy Performed for Upper Gastrointestinal Bleeding.

BACKGROUND: Although propofol-based sedation can be used during emergency endoscopy for upper gastrointestinal bleeding (UGIB), there is a potential risk of sedation-related adverse events, especially in patients with variceal bleeding. AIM: We compared adverse events related to propofol-based sedation during emergency endoscopy between patients with non-variceal and variceal bleeding. METHODS: Clinical records of patients who underwent emergency endoscopy for UGIB under sedation were reviewed. Adverse events, including shock, hypoxia, and paradoxical reaction, were compared between the non-variceal and variceal bleeding groups. RESULTS: Of 703 endoscopies, 539 and 164 were performed for non-variceal and variceal bleeding, respectively. Shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding (12.2 vs. 3.5%, P < 0.001). All patients except one recovered from shock after normal saline hydration, and emergency endoscopy could be finished without interruption in most cases. The incidence of hypoxia and paradoxical reaction did not differ based on the source of bleeding (non-variceal bleeding vs. variceal bleeding: hypoxia, 3.5 vs. 1.8%, P = 0.275; paradoxical reaction interfering with the procedure, 4.1 vs. 5.5%, P = 0.442). CONCLUSIONS: Although shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding, most cases could be controlled without procedure interruption. Paradoxical reaction, rather than shock or hypoxia, was the most common cause of procedure interruption in patients with variceal bleeding, but the rate did not differ between patients with non-variceal and variceal bleeding.

Life threatening biphasic adverse reactions to desmopressin: case report and review of the literature.

Treatment with desmopressin diacetate arginine vasopressin (DDAVP) and its withdrawal are associated with side effects. We present a rare case of severe biphasic adverse reactions induced by DDAVP and its withdrawal in a 63-year-old female patient. A lump in the left axillary region was biopsied, and she received DDAVP after surgery. The following day, she lost consciousness, with foaming at the mouth and seizures. Hypotonic encephalopathy was considered. DDAVP was ceased, and she received electrolytes. On day 1, she displayed low blood pressure and increased urine output. She received DDAVP and dopamine as well as electrolytes. The patient was ambulatory on day 7 and was discharged without brain abnormalities on MRI. In conclusion, severe hyponatremia induced by DDAVP and massive polyuria and hypovolemic shock induced by DDAVP withdrawal are life-threatening conditions. This case underlines the need to be vigilant when administering DDAVP and to monitor for any side effects.

Antipsychotics can induce pre-shock in very elderly patients: a report of two cases.

Antipsychotics have often been administered to treat delirium and intractable insomnia in elderly patients with or without dementia. However, antipsychotics sometimes cause severe adverse effects. We report two cases of very elderly patients who developed pre-shock after the administration of antipsychotics in a clinical consultation-liaison setting. These cases suggest that antipsychotics can induce fatal adverse events in very elderly patients. Although there has been little evidence regarding the most appropriate kind of drug and dosage for such patients, psychiatrists should exercise great caution in the use of antipsychotics for the very elderly, including deciding to prescribe the lowest dose or not prescribing them at all.

Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome.

Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse.