Bilateral Digital Ischemia Secondary to Heparin-Induced Thrombocytopenia with Subsequent Limb Salvage: A Case Study.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic state caused by the buildup of platelet factor 4 antibodies with decreased platelet count caused by heparin therapeutic or prophylactic therapy. It is important to detect this complication, especially in critically ill patients and cardiac patients. Detection of HIT can be demonstrated by positive antibodies in a HIT panel. Based on clinical and laboratory findings, heparin use should be discontinued with immediate transition to alternative anticoagulation therapies. Thromboembolic events can be an adverse effect of HIT and can cause local tissue necrosis, especially in the lower extremity. This case is a retrospective medical record review of a 52-year-old man who was initially admitted as an outpatient for coronary artery bypass grafting and mitral valve replacement who developed digital gangrene from HIT. This case emphasizes the rare adverse effects of HIT and the need for timely consultation for surgical treatment of limb ischemia/gangrene.

Aplicación de la cura en ambiente húmedo en la gangrena simétrica periférica asociada a fármacos vasoactivos para evitar amputación. Caso clínico / Healing in humid environment in symmetric peripheral gangrene associated with vasoactive drugs to avoid amputation. Clinical case

Objetivo: Exponer un abordaje terapéutico conservador para el abordaje de lesiones necróticas periféricas secundarias a la administración de fármacos vasoactivos. Metodología: A través de un caso clínico se describe el planteamiento de curas realizadas. Resultados: El caso se resolvió en 28 semanas y se evitó la amputación de todos los dedos de manos y pies, a excepción de 1 dedo de la mano y 2 dedos del pie, lo que minimizó las secuelas al paciente y se preservó su estado funcional. Conclusión: La aplicación en ambiente húmedo en este tipo de lesiones necróticas secundarias a fármacos vasoactivos, resultó efectiva en este caso clínico y evitó tratamientos más agresivos que pudieran repercutir negativamente en la calidad de vida del paciente (AU)

Objective: To present a conservative therapeutic approach for the approach of peripheral necrotic lesions secondary to the administration of vasoactive drugs. Methodology: Through a clinical case, the approach to cures carried out is described. Results: The case was resolved in 28 weeks avoiding the amputation of all fingers and toes except for 1 finger and 2 toes, minimizing the sequelae to the patient and preserving their functional status. Conclusion: The application of most environment treatment in this type of necrotic lesions secondary to vasoactive drugs was effective in this clinical case and avoided more aggressive treatments that could negatively affect the quality of life of the patient (AU)

Postoperative extremity gangrene in a patient with type 2 diabetes taking SGLT2 inhibitors: A case report.

RATIONALE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been approved and marketed since March 2013. The proportion of patients with type 2 diabetes (T2D) taking SGLT2 inhibitors is increasing. The perioperative adverse effects of SGLT2 inhibitors, especially euglycemic diabetic ketoacidosis (euDKA), should be taken into consideration in perioperative patient evaluation in both elective and emergency surgeries. PATIENT CONCERNS: A 57-year-old woman taking SGLT2 inhibitors for T2D developed euDKA after undergoing an emergency orthopedic surgery; the euDKA diagnosis was delayed, thereby causing extremity gangrene. DIAGNOSES: EuDKA was diagnosed based on the presence of strongly positive ketonuria, elevated blood beta-hydroxybutyrate level, and severe metabolic acidosis. INTERVENTION: EuDKA was treated with insulin infusion with dextrose solution and intravenous fluid resuscitation. OUTCOME: Due to a delayed diagnosis of euDKA, the patient received a high-dose vasopressor, which led to limb gangrene and amputation 6 months later. LESSONS: EuDKA is often misdiagnosed due to the absence of hyperglycemia. Serum beta-hydroxybutyrate levels or urinalysis could be used as screening tools for euDKA in patients scheduled for emergency surgery, in order to preoperatively administer rapid fluid resuscitation and insulin infusion with dextrose solution, which should continue postoperatively along with serum beta-hydroxybutyrate monitoring.

Acral vascular syndrome during an immune checkpoint inhibitor.

Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.

Symmetrical peripheral gangrene of bilateral feet and unilateral hand after administration of vasopressors during septic shock.

We report a case of a 75-year-old Hispanic man treated for septic shock after undergoing surgery for impacted renal stones. He was given vasopressors and later developed symmetrical peripheral gangrene (SPG) on both his feet and left hand. SPG is a serious and rare condition presenting clinically as an acute onset of ischaemia with no vessel occlusion. Vasopressors are identified as a contributing factor in SPG development. The patient ultimately underwent transmetatarsal amputations of both feet and amputation of three digits on his left hand. Early monitoring and swift management of peripheral ischaemia are essential when using vasopressors for the treatment of septic shock.

Risk Factors of Vasopressor-Induced Symmetrical Peripheral Gangrene.

BACKGROUND: Symmetrical peripheral gangrene (SPG) is an uncommon syndrome showing symmetrical gangrene in acral regions without evidence of large-vessel occlusion or vasculitis. Intravenous vasopressors are frequently used to manage hemodynamically unstable patients. There have been few reports about SPG after using inotropics. However, risk factors for SPG have not been extensively studied. Therefore, the objective of this study was to analyze several cases of SPG and identify risk factors for SPG. METHODS: From October 2013 to October 2016, 36 patients with SPG after using vasopressors were included in this study. SPG is an extremely rare disease entity. Therefore, this work was designed as a matched case-control study. For the control group, 42 patients (25 men and 17 women) with similar age, admission department, sex, and vasopressor usage in intensive care unit patients during the same period were selected. Retrospective chart review was performed to identify risk factors within the following categories: medical conditions, vasopressor-related factors, and Sequential Organ Failure Assessment scores. RESULTS: Differences between the 2 groups concerning medical condition-related variables did not exist. Statistically significant differences were found in intensive care unit duration (P = 0.0011) and survival. All vasopressor-related factors were adjusted according to weights of patients. Weight-compensated mean dose of dopamin significantly (P = 0.028) affected the occurrence of SPG. Weight-compensated peak dose of norpin, dopamin, and epinephrine also significantly contributed to SPG. CONCLUSIONS: Symmetrical peripheral gangrene is a rare clinical syndrome related with a high mortality and up to 70% of patients who survive require amputation. Several studies have mentioned that there are several factors affecting the result of SPG. Few studies on SPG have been reported and most of them are case reports. In this study, we revealed the influence of vasopressors to the occurrence of SPG, and this was the first matched case-control study based on the analysis of multiple risk factors.

Severe Hypernatremic Dehydration and Lower Limb Gangrene in an Infant Exposed to Lamotrigine, Aripiprazole, and Sertraline in Breast Milk.

BACKGROUND: Hypernatremic dehydration is well described in exclusively breastfed neonates, although life-threatening complications are rarely reported. MATERIALS AND METHODS: The present article describes a case of severe hypernatremic dehydration in a previously healthy term neonate. Other published cases of severe complications of hypernatremic dehydration are discussed. RESULTS: The exclusively breastfed neonate described had severe hypernatremic dehydration because of inadequate milk intake, with disseminated intravascular coagulation and right lower limb gangrene that required amputation of all five toes and surgical debridement of the metatarsals. The usual etiology of hypernatremic dehydration in this age group is insufficient breast milk intake. Here, the infant's mother was treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. CONCLUSIONS: Awareness of these complications should prompt close follow-up of the infant with poor weight gain. The role of maternal medication as a risk factor for hypernatremic dehydration among exclusively breastfed infants needs to be further explored.

[Gangrene of the hand due to accidental intra-arterial injection of floxacilline: about a case]. / Gangrène de la main après injection accidentelle intra artérielle de floxacilline: à propos d'un cas.

Floxacilline is a beta-lactam antibiotic of the penicillin class. In our context it is used to fight against infections caused by gram-positive bacteria, including staphylococcus aureus. However, floxacilline should be administered with great caution due to its possible side-effects. Our study reports the case of a 6-year old boy who underwent surgery for the treatment of a humeral fracture. The child was treated with injectable floxacilline following a suspected orthopaedic device infection 2 months after surgery. The day after starting antibiotic treatment, the child presented with acute ischemia of the right hand. Then, he was referred to us. Explorations objectified occlusion of the radial artery. The patient underwent relieving fasciotomy and received postoperative heparin. The evolution was marked by gangrene affecting the whole hand. The aim of our study was to educate caregivers about the risk of occurrence of this disastrous complication and about the measures to prevent it.

Safety of Epinephrine in Digital Nerve Blocks: A Literature Review.

BACKGROUND: Digital nerve blocks are commonly performed in emergency departments. Health care practitioners are often taught to avoid performing blocks with epinephrine due to a risk of digital necrosis. OBJECTIVE: To review the literature on the safety of epinephrine 1:100,000-200,000 (5-10 µg/mL) with local anesthetics in digital nerve blocks in healthy patients and in patients with risk for poor peripheral circulation. METHODS: PubMed, Web of Science, and the Cochrane Library were searched in June 2014 using the query "digital block AND epinephrine OR digital block AND adrenaline". The searches were performed without any limits. RESULTS: Sixty-three articles were identified, and 39 of these were found to be relevant. These include nine reviews, 12 randomized control trials, and 18 other articles. Most studies excluded patients with risk for poor peripheral circulation. Two studies described using epinephrine on patients with vascular comorbidities. No study reported digital necrosis or gangrene attributable to epinephrine, either in healthy patients or in patients with risk for poor peripheral circulation. In total, at least 2797 digital nerve blocks with epinephrine have been performed without any complications. CONCLUSIONS: Epinephrine 1:100,000-200,000 (5-10 µg/mL) is safe to use in digital nerve blocks in healthy patients. Physiological studies show epinephrine-induced vasoconstriction to be transient. There are no reported cases of epinephrine-induced harm to patients with risk for poor peripheral circulation despite a theoretical risk of harmful epinephrine-induced vasoconstriction. A lack of reported complications suggests that the risk of epinephrine-induced vasoconstriction to digits may be overstated.

The wacky hypercoagulable state of malignancy.

In this issue of Blood, Warkentin et al describe a novel clinical syndrome of warfarin-associated severe venous limb ischemia occurring in a series of 10 patients with malignancy after initiating treatment of deep venous thrombosis. Patients in this series also demonstrated a decline in platelet counts after stopping heparin, warfarin-associated supratherapeutic international normalized ratios (INRs), and evidence of persistent thrombin generation despite anticoagulation.

Complicating Symmetric Peripheral Gangrene after Dopamine Therapy to Patients with Septic Shock.

Dopamine is commonly used as a first-line agent in the treatment of patients with septic shock. The use of dopamine rarely causes symmetric peripheral dry gangrene. If the symmetric peripheral dry gangrene occurs in the patient after dopamine injection, it easily leads to disagreement between doctors and patients. A 60-year-old woman who had sudden septic shock was sent to intensive care unit (ICU). She was received dopamine injection according to the routine during treatment. Over the next 3 months, her limbs developed to dry gangrene and required amputation. The result shows that the occurrence of dry gangrene could only be associated with the long-term excessive use of dopamine according to the medical records. Although dopamine is a conventional drug for the treatment of septic shock, the forensic workers and clinicians must realize that vasopressors such as dopamine have been implicated directly or as a contributory cause in dry gangrene cases.

Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome.

Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patients, cancer was not known or suspected at presentation. The patients exhibited a novel, clinically distinct syndrome: warfarin-associated supratherapeutic international normalized ratio (INR; median, 6.5) at onset of limb ischemia, rising platelet count during heparin anticoagulation, and platelet fall after stopping heparin. Despite supratherapeutic INRs, patient plasma contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this profile resembles the greatly elevated TAT/PC activity ratios reported in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients with available serial plasma samples showed that variations in the INR corresponded most closely with changes in factor VII, with a highly collinear relationship between VII and PC. We conclude that venous limb ischemia/gangrene is explained in some cancer patients by profoundly disturbed procoagulant-anticoagulant balance, whereby warfarin fails to block cancer-associated hypercoagulability while nonetheless contributing to severe PC depletion, manifest as a characteristic supratherapeutic INR caused by parallel severe factor VII depletion.

[Perineoscrotal gangrene after a snake bite: a case report]. / Un cas de gangrène périnéoscrotale consécutive à une morsure de serpent.

The authors describe a case of perinoscrotal gangrene in a patient who had been bitten by a snake. He was treated with antivenom immunotherapy and surgery. The outcome was good. They present a brief review of the literature regarding the epidemiological, clinical, and treatment issues.

The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity.

"Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis. In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution.

Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study.

BACKGROUND: The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes. METHODS: We identified all patients living in Denmark who were aged 40 years or older and were diagnosed with incident diabetes between Jan 1, 1996, and Dec 31, 2009. We obtained patients' data from the Danish Patient Registry and information on drug use from the Danish Registry of Medicinal Product Statistics. We randomly selected 15,679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47,037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address potential biases between statin users and non-statin users, we made adjustments to our analysis with a propensity score and with other factors. Median follow-up was 2·7 years (range 0-13). FINDINGS: During 215,725 person-years of follow-up, 2866 patients developed diabetic retinopathy, 1406 developed diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54-0·66; p<0·0001), diabetic neuropathy (0·66, 0·57-0·75; p<0·0001), and gangrene of the foot (0·88, 0·80-0·97; p=0·010), but not diabetic nephropathy (0·97, 0·85-1·10; p=0·62). These results were similar after adjusting for the competing risk of death, after matching for a propensity score, after adjusting for visits to a family doctor, and by stratification on covariates. The corresponding multivariable adjusted hazard ratio for risk of diabetes in the total population was 1·17 (95% CI 1·14-1·21; p<0·0001). INTERPRETATION: Use of statins before diagnosis of incident diabetes was not associated with an increased risk of microvascular disease. Whether statins are protective against some forms of microvascular disease-a possibility raised by these data-will need to be addressed in other studies similar to ours, in mendelian randomisation studies, and preferably in randomised controlled trials. FUNDING: Herlev Hospital, Copenhagen University Hospital.