A clinical classification system for grading platinum hypersensitivity reactions.

OBJECTIVES: Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice. METHODS: This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (>10 min) were used to define severe reaction. Fischer Exact Tests (p < .05) and binary logistic regression analyses were performed. Spearman correlation were used to assess relationships between our grading system and the NCCN and CTCAEv4.0 criteria. RESULTS: 87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148-87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263-55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026-142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815-512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p < .001). CONCLUSIONS: This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.

Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

The Incidence of and Risk Factors for Postintubation Hypotension in the Immunocompromised Critically Ill Adult.

OBJECTIVES: Our primary aim was to ascertain the frequency of postintubation hypotension in immunocompromised critically ill adults with secondary aims of arriving at potential risk factors for the development of postintubation hypotension and its impact on patient-related outcomes. METHODS: Critically ill adult patients (≥18 years) were included from January 1, 2010, to December 31, 2014. We defined immunocompromised as patients with any solid organ or nonsolid organ malignancy or transplant, whether solid organ or not, requiring current chemotherapy. Postintubation hypotension was defined as a decrease in systolic blood pressure to less than 90 mm Hg or a decrease in mean arterial pressure to less than 65 mm Hg or the initiation of any vasopressor medication. Patients were then stratified based on development of postintubation hypotension. Potential risk factors and intensive care unit (ICU) outcome metrics were electronically captured by a validated data mart system. RESULTS: The final cohort included 269 patients. Postintubation hypotension occurred in 141 (52%; 95% confidence interval: 46-58) patients. Several risk factors predicted postintubation hypotension on univariate analysis; however, only Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability remained significant on all 4 multivariate analyses. Patients developing postintubation hypotension had higher ICU and hospital mortality (54 [38%] vs 31 [24%], P = .01; 69 [49%] vs 47 [37%], P = .04). CONCLUSION: Based on previous literature, we found a higher frequency of postintubation hypotension in the immunocompromised than in the nonimmunocompromised critically ill adult patients. Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability were significant predictors on multivariate analyses. Postintubation hypotension led to higher ICU and hospital mortality in those experiencing this complication.

Cardiotoxicity of Immunotherapy: Incidence, Diagnosis, and Management.

PURPOSE OF REVIEW: This review describes cardiotoxicity associated with adoptive T cell therapy and immune checkpoint blockade. RECENT FINDINGS: Cardiotoxicity is a rare but potentially fatal complication associated with novel immunotherapies. Both affinity-enhanced and chimeric antigen receptor T cells have been reported to cause hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Immune checkpoint inhibitors are generally well-tolerated but have the potential to cause myocarditis, with clinical presentations ranging from asymptomatic cardiac biomarker elevation to heart failure, arrhythmia, and cardiogenic shock. Electrocardiography, cardiac biomarker measurement, and cardiac imaging are key components of the diagnostic evaluation. For suspected myocarditis, endomyocardial biopsy is recommended if the diagnosis remains unclear after initial testing. The incidence of immunotherapy-associated cardiotoxicity is likely underestimated and may increase as adoptive T cell therapy and immune checkpoint inhibitors are used in larger populations and for longer durations of therapy. Baseline and serial cardiac evaluation is recommended to facilitate early identification and treatment of cardiotoxicity.

Clinical Evaluation of "Shock Bowel" Using Intestinal Fatty Acid Binding Protein.

"Shock bowel" is one of the computed tomographic (CT) signs of hypotension, yet its clinical implications remain poorly understood. We evaluated how shock bowel affects clinical outcomes and the extent of intestinal epithelial damage in trauma patients by measuring the level of intestinal fatty acid binding protein (I-FABP). We reviewed the initial CT scans, taken in the emergency room, of 92 patients with severe blunt torso trauma who were consecutively admitted during a 24-month period. The data collected included CT signs of hypotension, I-FABP, feeding intolerance, and other clinical outcomes. Demographic and clinical outcomes were compared in patients with and without hemodynamic shock and shock bowel. Shock bowel was found in 16 patients (17.4%); of them 7 patients (43.8%) did not have hemodynamic shock. Certain CT signs of hypotension, namely free peritoneal fluid, contrast extravasation, small-caliber aorta, and shock bowel, were significantly more common in patients with hemodynamic shock than in patients without (P < 0.05). Injury severity score and the rate of consciousness disturbance were significantly higher in patients with shock bowel than in patients without (P < 0.05). The rate of feeding intolerance and median plasma I-FABP levels were significantly higher in patients with shock bowel than in patients without (75.0% vs. 22.4%, P < 0.001 and 17.0 ng/mL vs. 3.7 ng/mL, P < 0.001, respectively). There was no difference in mortality. In conclusion, shock bowel is not always due to hemodynamic shock. It does, however, indicate severe intestinal mucosal damages and may predict feeding intolerance.

Takotsubo cardiomyopathy caused by epinephrine-treated bee sting anaphylaxis: a case report.

INTRODUCTION: Stress-induced cardiomyopathy (Takotsubo) after bee stings in patients who have received catecholamines is rare. Endogenous as well as exogenous administration of catecholamines is thought to trigger stress-induced cardiomyopathy. CASE PRESENTATION: A 37-year-old healthy white woman was stung by an unknown Hymenoptera that resulted in an anaphylactic reaction. Intravenous adrenaline (0.9 mg) was administered at a nearby clinic; she was transferred to our emergency room. Cardiogenic shock was diagnosed and mechanical ventilation commenced. Hemodynamic stabilization was not achieved by inotropic support and intra-aortic balloon pump insertion. Initial coronary angiography did not demonstrate any coronary obstructive lesions while her left ventricular systolic function was severely depressed. Peripheral femoral venoarterial extracorporeal membrane oxygenation was inserted as a bridge to recovery assuming possible reversible cause of the cardiogenic shock. Over the following 48 hours she was extubated and gradually weaned off venoarterial extracorporeal membrane oxygenation and inotropic support. She was discharged with a near normal left ventricular ejection fraction and in 3 weeks she was asymptomatic with normal electrocardiographic and echocardiographic examinations (left ventricular ejection fraction >65 %). CONCLUSIONS: A Hymenoptera sting may be a specific cause of catecholamine cardiac depression. The presence of cardiogenic shock and its etiology should prompt aggressive management including extracorporeal membrane oxygenation as a bridge to cardiac functional recovery in such rare scenarios.

Time of Onset and Predictors of Biphasic Anaphylactic Reactions: A Systematic Review and Meta-analysis.

BACKGROUND: A biphasic reaction is a potentially life-threatening recurrence of symptoms after initial resolution of anaphylaxis without re-exposure to the trigger. The infrequent nature of these reactions has made them difficult to study and predict. OBJECTIVE: The aim of this study was to evaluate the time of onset and predictors of biphasic anaphylactic reactions. METHOD: Original research studies that described biphasic reactions in case series or cohort studies were included. Studies that did not describe biphasic reactions and case series with less than 2 biphasic reactions were excluded. Data sources included MEDLINE, EMBASE, Web of Science, and Scopus from inception to January 2014 and bibliographies of included articles. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous variables. Inconsistency among studies was assessed with the I(2) statistic. RESULTS: Twenty-seven observational studies that enrolled 4114 patients with anaphylaxis and 192 patients with biphasic reactions were included. The median time of symptom onset was 11 (range 0.2 to 72.0) hours. Food as the inciting trigger was associated with decreased risk (pooled OR 0.62, 95% CI: 0.4 to 0.94, I(2) = 0%) and an unknown inciting trigger with increased risk (pooled OR 1.72, 95% CI: 1.0 to 2.95, I(2) = 61%). Initial presentation with hypotension (pooled OR 2.18, 95% CI: 1.14 to 4.15, I(2) = 79%) was also associated with the development of a biphasic reaction. CONCLUSION: Biphasic anaphylatic reactions were less likely among patients with food as an inciting trigger. Patients who present with hypotension or have an unknown inciting trigger may be at increased risk of a biphasic reaction. Clinicians should tailor observation periods for patients individually based on clinical characteristics.

Features of complement activation-related pseudoallergy to liposomes with different surface charge and PEGylation: comparison of the porcine and rat responses.

Pigs are known to provide a sensitive model for studying complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction to liposomal and many other nanomedicines that limits their clinical use. The utility of rats as a CARPA model has, however, not been analyzed to date in detail. The present study compared the two models by inducing CARPA with i.v. bolus injections of two reactogenic liposomes that differed from each other in surface properties: one was AmBisome, a strong anionic, free-surface small unilamellar liposome (SUV), while the other was neutral, polyethylene glycol (PEG)-grafted SUV wherein the 2 kDa-PEG was anchored to the membrane via cholesterol (Chol-PEG). Both in pigs and rats AmBisome caused significant consumption of C3, indicating C activation, along with paralleling massive changes in blood pressure, white blood cell, platelet counts and in plasma thromboxane B2 levels, indicating CARPA. These processes were similar in the two species in terms of kinetics, but significantly differed in the doses that caused major hemodynamic changes (~0.01 and ~22 mg phospholipid (PL)/kg in pigs and rats, respectively). Pigs responded to AmBisome with pulmonary hypertension and systemic hypotension, and the reaction was not tachyphylactic. The major response of rats was systemic hypotension, leukopenia followed by leukocytosis, and thrombocytopenia. Chol-PEG liposomes caused severe reaction in pigs at 0.1 mg/kg, while the reaction they caused in rats was mild even at 300 mg PL/kg. Importantly, the reaction to Chol-PEG in pigs was partly tachyphylactic. These observations highlight fundamental differences in the immune mechanisms of porcine and rat CARPA, and also show a major impact of liposome surface characteristics, determining the presence or absence of tachyphylaxis. The data suggest that rats are 2-3 orders of magnitude less sensitive to liposomal CARPA than pigs; however, the causes of these differences, the PEG-dependent tachyphylaxis and the massive reactivity of Chol-PEG liposomes remain unclear.

Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats.

Hypotension is a physiologic state of low blood pressure, the causes of which range from dehydration to underlying serious medical disorders. The aim of this study was to assess the utility of lactoferrin (LF), a natural immunomodulator, to restrain LPS-induced hypotension in rats. LF has previously demonstrated a role in mediation of immune responses, including control of inflammatory cytokine production during acute inflammation. Rats were administered with LF by gavage at 1h or 18 h prior to LPS injections. Heart rate (HR) and mean arterial blood pressure (MAP) were continuously recorded post LPS administration for 6 h. Simultaneously to hemodynamic measurements, serum was examined for TNF-α, IL-6, and TGF-ß production. At termination, the proximal duodenum was subjected to histopathological analysis. LF administered at 1h prior to LPS protected rats from the LPS-induced hypotension. The protective effect on MAP was also apparent when LF was administered as a pretreatment 18 h prior to LPS challenge, although the effect was lessened. For all groups, LF pretreatment led to a minor, but insignificant, improvement in HR post LPS administration. In addition, when rats were given LF 1 h before LPS, they showed a significant decrease in serum TNF-α and IL-6 production. LF did not affect the production level of serum TGF-ß. Of high importance, LF was able to confer histo-pathological protection of intestinal tissue post LPS administration, for both the 1h and 18 h LF pretreatment groups. These studies indicate a potential for clinical utility of LF to control hypotension.

Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension.

BACKGROUND: Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures.We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures. METHODS: Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance. RESULTS: A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p < 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p < 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p < 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial. CONCLUSIONS: We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin. TRIAL REGISTRATION: ISRCTN 20957055.

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft.

The objectives of this prospective, observational study were (1) to determine whether a transplanted liver graft releases proinflammatory cytokines into the systemic circulation upon reperfusion and (2) to determine whether they contribute to any subsequent hemodynamic instability observed after graft reperfusion (if this release occurs). Blood samples from 17 consecutive patients undergoing liver transplantation were analyzed for cytokines, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), IL-2, IL-6, and IL-8. Blood samples were obtained from the radial artery, portal vein, and flush blood (a sample taken from a catheter placed above the infrahepatic inferior vena cava clamp). The amount of catecholamines necessary to maintain a mean arterial pressure between 65 and 75 mm Hg during graft reperfusion was compared with the level of cytokines. A statistical analysis was performed with the least squares method, Kendall's tau-b test, and regression analysis. We demonstrated that flush blood from the liver grafts contained a significant amount and variety of cytokines. Most of these were removed by graft irrigation. The concentration of TNF-α in samples obtained from flush blood at the end of liver irrigation was significantly higher than the concentration in samples obtained from the radial artery (P = 0.0067) or portal vein (P = 0.0003) before reperfusion. This correlated directly with the amount of catecholamines used to treat hemodynamic instability. Although there were increased levels of IL-1ß, IL-2, and IL-8 in the flush blood, there was no statistically significant correlation between the levels of these cytokines and the amount of catecholamines used.

[Peanut allergy]. / Alergia la arahide.

Peanut allergy currently affects around 1% of the UK and US paediatric population and represents a major healthcare concern because it is outgrown in less than 20% of cases and is a major cause of anaphylaxis. Its main symptoms, triggered by peanut ingestion, are cutaneous (urticaria, erythema, angioedema), gastrointestinal (abdominal pain, vomiting, diarrhoea), respiratory (wheezing, dyspnoea) and cardiovascular (hypotension, arrhythmia, shock). The usual onset of symptoms occurs soon after peanut ingestion (minutes to hours); however some patients have biphasic reactions, with exacerbations occurring up to 8 hours later. Peanut allergy diagnostic is based mainly upon the medical history (preferably including a diet diary and elimination diets), skin testing, peanut-specific IgE measurement and ideally a peanut oral challenge. Peanut allergy management includes monitorisation and education for avoiding peanut-containing foods and for recognising and treating anaphylactic episodes (self-injectable adrenalin and rapid-acting antihistamines). In the past, anti-IgE antibodies were shown to decrease the risk of anaphylaxis by reducing the allergic patients' reactivity to peanuts. Recent investigations, driven by the need to develop efficient treatment and prevention strategies for peanut allergy, suggest that oral immunotherapy with peanuts, although exposing the patients to significant risk, may represent a promising therapeutic approach. Furthermore, contrary to the general view that peanut avoidance in infants could prevent peanut allergy, a recent study shows that the opposite may be true as early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy.

Preoperative heparin therapy causes immune-mediated hypotension upon heparin administration for cardiac surgery.

OBJECTIVE: To evaluate whether patients with positive or negative heparin antibodies who received heparin preoperatively by continuous infusion developed cardiovascular changes upon heparin administration prior to cardiopulmonary bypass. DESIGN: Clinical trial. SETTING: Single institution, academic hospital. PARTICIPANTS: Eighty (80) patients with good ventricular function on low-dose heparin infusion prior to surgery. INTERVENTIONS: Patients were divided into 2 equal groups: group A had negative heparin antibodies (% ratio < 0.26), group B had positive heparin antibodies (% ratio > 1.2). All patients received heparin, 400 units/kg, prior to institution of cardiopulmonary bypass. Cardiovascular changes, activated coagulation time (ACT), and histamine levels were measured before and 5 minutes after administration of heparin. Platelets also were counted before and 6 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Significant hypotension and decreased cardiac index occurred in patients with positive heparin antibodies who received heparin prior to cardiac surgery. Histamine levels increased significantly 5 minutes after heparin administration. Significant thrombocytopenia occurred 6 hours after surgery in group B patients. There was a good correlation between heparin antibodies, histamine levels, thrombocytopenia and cardiovascular changes. Group B patients also had heparin resistance as manifested by a lower ACT after the loading doses of heparin. CONCLUSION: Patients with positive heparin antibodies pretreated with heparin prior to surgery developed a type of immune-mediated cardiovascular changes and postoperative thrombocytopenia.

Suspected recurrent anaphylaxis in different forms during general anesthesia.

We report on a patient who presented with recurrent severe shock during general anesthesia. The patient was a man scheduled for lung surgery whose first attack was a coronary spasm, which was followed by a second shock with severe bronchospasm and hypotension 4 weeks later. An elevated serum tryptase concentration was observed, and subsequent skin testing revealed negative reactions to some drugs administered in this case. This case serves to alert anesthetists to the possibility of some different forms of allergy and highlights the importance of rigorous investigation of all the reagents and phenomena.

Contribution of vasoactive eicosanoids and nitric oxide production to the effect of selective cyclooxygenase-2 inhibitor, NS-398, on endotoxin-induced hypotension in rats.

Our previous studies with the use of non-selective cyclooxygenase (COX) inhibitor, indomethacin, demonstrated that prostanoids produced during endotoxaemia increase inducible nitric oxide synthase (iNOS) protein expression and nitric oxide synthesis, and decrease cyctochrome P450 (CYP) 4A1 protein expression and CYP 4A activity. The results suggest that dual inhibition of iNOS and COX by indomethacin restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from CYP 4A in endotoxaemic rats. The present study examined whether increased levels of vasoconstrictor eicosanoids, 20-HETE, prostaglandin F(2α) (PGF(2α) )and thromboxane A(2) (TxA(2) ), would contribute to the effect of selective COX-2 inhibition to prevent endotoxin (ET)-induced fall in blood pressure associated with an increase in the production of vasodilator prostanoids, prostaglandin I(2) (PGI(2) ) and prostaglandin E(2) (PGE(2) ) and nitric oxide synthesis. Mean arterial blood pressure fell by 31 mmHg and heart rate (HR) rose by 90 beats/min. in male Wistar rats treated with ET (10 mg/kg, i.p.). The fall in mean arterial pressure and increase in HR were associated with increased levels of 6-keto-prostaglandin F(1α) (6-keto-PGF(1α) ), PGE(2) , TxB(2) , and nitrite in the serum, kidney, heart, thoracic aorta and/or superior mesenteric artery. Systemic and renal 20-HETE and PGF(2α) levels were also decreased in endotoxaemic rats. These effects of ET were prevented by a selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)methansulphonamide (10 mg/kg, i.p.), given 1 hr after injection of ET. These data suggest that an increase in 20-HETE and PGF(2α) levels associated with decreased production of PGI(2) , PGE(2) , and TxA(2) , and nitric oxide synthesis contributes to the effect of selective COX-2 inhibitor to prevent the hypotension during rat endotoxaemia.

Elevated serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions.

BACKGROUND: Anaphylaxis is generally unanticipated and requires emergency management. Therefore, the biological mediators in human beings have been difficult to define. OBJECTIVE: Our aim was to identify cytokines and chemokines whose concentrations increase during anaphylaxis in human beings and to determine how each correlates with severity. METHODS: We measured the concentrations of potential mediators, including cytokines, chemokines, mast cell tryptase (MCT), and histamine, over 3 time points in 76 patients presenting to emergency departments with anaphylaxis and correlated these with a global severity scale, hypotension, and hypoxia. RESULTS: IL-2, IL-6, IL-10, TNF receptor I, MCT, and histamine were significantly elevated in patients with severe reactions (n = 36) compared with moderate reactions (n = 40) and healthy controls. Histamine levels peaked at emergency department arrival, whereas other mediators peaked later. IL-4, IL-5, IL-13, IFN-gamma, and TNF-alpha were marginally elevated in severe reactions compared with healthy controls but did not correlate with reaction severity. Severe reactions tended to be either hypotensive (n = 19) or hypoxemic (n = 12). Levels of IL-6, IL-10, TNF receptor I, MCT, and histamine correlated with hypotension. No mediator correlated with hypoxemia or other respiratory features. CONCLUSION: This study confirms that the concentrations of a number of cytokines are elevated in blood during anaphylaxis in human beings and that some correlate with the presence of hypotension. Others were only marginally elevated within a concentration range that available assays do not reliably detect. During respiratory reactions, mediators may be largely confined to the airways so that blood concentrations do not reflect activity.

Protamine-associated hypotension in patients on hemodialysis: retrospective study and prevalence of antiprotamine antibodies.

AIMS: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects. METHOD: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients. RESULTS: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31). CONCLUSIONS: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Hepatic microvascular pressure during anaphylactic shock in anesthetized rats.

OBJECTIVE: Hepatic venoconstriction plays a significant role in anaphylactic hypotension in anesthetized rats. The purpose of this study is to determine whether the primary site of anaphylactic venoconstriction in the liver venous circulation occurs prior to or distal to the sinusoidal capillaries. We also determined whether the hepatic blood volume is increased during anaphylactic hypotension. METHODS: We measured, using a servo-null micropipette pressure-measuring system, the hepatic venular transmural pressure (P micro hv) at the liver surface of anesthetized rats sensitized with the antigen of ovalbumin (1 mg). We also measured the liver lobe thickness, using the ultrasonic crystal dimension measuring system. Anaphylactic hypotension was induced by an intravenous injection of 0.6 mg ovalbumin. RESULTS: When the antigen was injected, the systemic arterial pressure decreased profoundly from 118+/-9 to 45+/-4 mm Hg, which was accompanied by an increase in Ppv and P micro hv: P micro hv only transiently increased from 3.1+/-0.9 to 8.8+/-1.5 cm H(2)O at 1 min and then rapidly returned to the baseline within 2 min, when Ppv continued to increase and reached the peak of 36+/-7 cm H(2)O at 3.5 min after antigen. This greater increase in Ppv-to-P micro hv gradient than that in P micro hv-to-Pcv gradient after antigen indicated that the constriction of the portal veins and the sinusoids much predominates over that of the hepatic veins. Along with this hepatic pre- and sinusoidal constriction, the liver lobe thickness significantly decreased by 4% after antigen. CONCLUSION: Pre-sinusoidal constriction during anaphylactic shock in anaesthetized rats increased the portal venous pressure while the hepatic venular pressure only increased slightly and transiently. This predominant pre-sinusoidal constriction is accompanied by a decrease in liver volume.