Treatment with a platelet‐activating factor receptor antagonist improves hemodynamics and reduces epinephrine requirements, in a lethal rodent model of anaphylactic shock

Abstract

Background In some cases, anaphylactic shock (AS) is still lethal, despite rapid use of epinephrine. High doses of epinephrine are associated with severe complications. Platelet‐activating factor (PAF) is secreted in massive amounts during AS, and a high plasma level is correlated with increased AS severity. Objective To assess the effect of ABT‐491, a PAF‐receptor antagonist and possible adjunct treatment, alone or in combination with epinephrine during AS. Methods AS was induced by intravenous injection of 1 mg ovalbumin into ovalbumin‐sensitized rats. Rats were then randomly assigned to 5 groups (n = 10 per group): SHAM (vehicle only), SHOCK (no treatment), ABT (ABT‐491 1 mg/kg), EPI (epinephrine 5 µg as a bolus then 10 µg kg−1 min−1 by continuous infusion, followed by a reducing protocol) and EPI‐ABT (both treatments). Results Ovalbumin injection resulted in a severe decrease in mean arterial pressure, left ventricular inotropy (max dP/dt) and left ventricular shortening fraction (LVSF). All rats from the ABT group survived until the end of the experiment. ABT‐491 prevented the LVSF decrease observed in the SHOCK group (at T15: ABT 50% ± 11% vs SHOCK 36% ± 9%, P = .01), significantly reduced the dose of epinephrine needed to treat anaphylactic shock (EPI‐ABT 314 ± 67 µg/kg vs EPI 475 ± 69 µg/kg, P < .001) and reduced the time to restore basal MAP (ABT 23 ± 7 minutes vs EPI‐ABT 13 ± 5 minutes, P < .01). Conclusions and Clinical Relevance AS was characterized by early cardiac dysfunction in our model. Treatment with ABT‐491 allowed survival until the end of the experiment and reduced cardiac dysfunction. Use of the PAF‐R antagonist had a synergistic effect with epinephrine and allowed a significant reduction in epinephrine consumption. Use of PAF‐R antagonists during AS could reduce epinephrine‐related complications and improve the treatment of epinephrine refractory cases.

Epidemiology and outcome of patients admitted to intensive care after anaphylaxis in France: a retrospective multicentre study

“…fluids should be rapid, within 1 h of onset of anaphylaxis. 25,26 Hypovolaemia occurs within minutes after onset of anaphylaxis and is often profound, with severe reduction in tissue perfusion. 26,27 Volume loading with crystalloids is recommended, but may not be effective in restoring cardiac preload because of persistent high vascular leakage and vascular hyporesponsiveness.…”

“…25,26 Hypovolaemia occurs within minutes after onset of anaphylaxis and is often profound, with severe reduction in tissue perfusion. 26,27 Volume loading with crystalloids is recommended, but may not be effective in restoring cardiac preload because of persistent high vascular leakage and vascular hyporesponsiveness. 26 Colloids, if not suspected of being a trigger for anaphylaxis, could be used as second-line therapy in cases of persistent hypovolaemia.…”

“…26,27 Volume loading with crystalloids is recommended, but may not be effective in restoring cardiac preload because of persistent high vascular leakage and vascular hyporesponsiveness. 26 Colloids, if not suspected of being a trigger for anaphylaxis, could be used as second-line therapy in cases of persistent hypovolaemia. Clinical data are lacking on which type of colloid should be used.…”

Developments in the field of allergy in 2020 through the eyes of Clinical and Experimental Allergy

“…Other work covered the issue of product availability for venom immunotherapy in the UK, 115 epidemiology of allergic and respiratory disease 116‐119 , 120 , 121 occupational allergies, 122‐124 advances in allergy diagnostics 125‐133 , 134 , 135 , 136 , animal model work 137 138 , 139 , 140 , 141 , investigation of infant airway epithelium, 142 a possible association between tree pollen exposure and reduced lung function 143 and evaluations of allergy service delivery 144‐147 …”

Severe wheeze, aspergillus and a new approach for anaphylaxis

“…Finally, Tacquard et al have looked at a novel approach to treating severe anaphylaxis in an animal model . ABT‐491, a platelet activating factor (PAF)‐receptor antagonist, was given with or without adrenaline.…”