Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats.

PURPOSE: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. AIM OF THE STUDY: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. MATERIALS AND METHODS: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. RESULTS: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L-1 vs. vehicle 52 ± 8 hPa.s.L-1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L-1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L-1; p = 0.42). CONCLUSIONS: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Epinephrine, compared with arginine vasopressin, is associated with similar haemodynamic effects but significantly improved brain oxygenation in the early phase of anaphylactic shock in rats: An experimental study.

BACKGROUND: In contrast to other types of shock, anaphylactic shock decreases cerebral blood flow more than would be expected from severe arterial hypotension, thus potentially affecting survival through brain ischaemia/hypoxia. We hypothesised that epinephrine (EPI) used as a first-line treatment of anaphylactic shock and arginine vasopressin (AVP) proposed in case of EPI refractoriness may have different effects on brain oxygenation. OBJECTIVES: To compare the effect of EPI and AVP on brain oxygenation under similar macro-haemodynamic target values in an anaphylactic shock model. DESIGN: Prospective laboratory study. SETTING: University laboratory. ANIMALS: Male brown Norway rats (n = 27). INTERVENTIONS: Twenty-seven rats were sensitised with ovalbumin (OVA). Twenty rats had anaphylactic shock induced with OVA and were resuscitated with either 0.9% saline (OVA group), EPI (EPI group) or AVP (AVP group). Sensitised control rats received only 0.9% saline and no OVA (CON group). MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), carotid artery blood flow (CaBF), cerebral cortical blood flow (CBF) and hippocampal oxygen partial pressure (PtiO2) were recorded. RESULTS: All rats in the OVA group died within 15 min. EPI and AVP restored comparable levels of MAP, carotid artery blood flow and CBF, and extended survival time. EPI was associated with biologically relevant and significantly (P < 0.05) higher PtiO2 values (nadir values at 20 min: 25.0 ± 2.2 mmHg) compared with the AVP group (14.9 ± 2.0 mmHg). The slopes of the correlations of MAP vs. PtiO2 and CBF were significantly steeper with AVP (more pressure dependence) compared with EPI. By the end of the experiment, hippocampal PtiO2 values between the EPI (24.1 ± 2.1 mmHg) and the AVP (20.8 ± 2.0 mmHg) groups were similar. CONCLUSION: At early, but not at late time points, resuscitation of anaphylactic shock with EPI or AVP to similar MAP and CBF endpoints resulted in hippocampal PtiO2 being significantly higher after EPI. In addition, the PtiO2 after EPI always remained above the threshold for brain hypoxia, whereas PtiO2 after AVP was below the hypoxic threshold most of the time. Because of this early brain hypoxia, AVP may not be the drug of first choice for resuscitation of anaphylactic shock.

Methylene blue and epinephrine: a synergetic association for anaphylactic shock treatment.

BACKGROUND: Severe hypotension resulting from anaphylactic shock may be refractory to epinephrine and impair cerebral oxygenation and metabolism contributing to anaphylactic shock morbidity and mortality. Refractoriness to epinephrine could be corrected by nitric oxide pathway inhibitors such as methylene blue. OBJECTIVES: To compare the systemic and regional (brain and skeletal muscle) effects of epinephrine and methylene blue given alone or in combination in a rat model of anaphylactic shock. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Male Brown-Norway rats (n = 60). INTERVENTIONS: After sensitization and induction of anaphylactic shock by ovalbumin, animals received either vehicle (ovalbumin group) or a 3-mg/kg methylene blue bolus (methylene blue group) or epinephrine (epinephrine group) or both (methylene blue-epinephrine group). Sensitized control rats received only vehicle and no ovalbumin (control group). MEASUREMENT AND MAIN RESULTS: Mean arterial pressure, cardiac output, cerebral blood flow, skeletal muscular oxygen partial pressure, cerebral oxygen partial pressure, skeletal muscular, and cerebral interstitial lactate/pyruvate ratio were measured. Cleaved caspase 3 and hypoxia-inducible factor-1α expression were analyzed in the cerebral cortex by Western blot. Without treatment, rats died rapidly within 15 mins from a decrease in cardiac output and mean arterial pressure, whereas treated rats survived until the end of the experiment. Methylene blue alone extended survival time but without significant improvement of hemodynamic variables and tissue perfusion and did not prevent neuronal injury. Epinephrine restored partially systemic hemodynamic variables and cerebral perfusion preventing glutamate-induced excitotoxicity. Compared with epinephrine alone, the methylene blue-epinephrine association avoided neuronal excitotoxicity and had an additive effect both on hemodynamic variables and for prevention of brain ischemia. Neither treatment could significantly restore cardiac output or prevent muscular compartment ischemia and microvascular leakage. CONCLUSIONS: Anaphylactic shock is associated with severe impairment of cerebral blood flow despite correction of arterial hypotension. Epinephrine must still be considered as the first-line vasoconstrictive agent to treat anaphylactic shock. The epinephrine-methylene blue association was the most effective treatment to prevent cerebral ischemia and could be used in anaphylactic shock refractory to epinephrine.

Anaphylactic shock decreases cerebral blood flow more than what would be expected from severe arterial hypotension.

The effects of acute reduction in arterial blood pressure in severe anaphylactic shock (AS) on cerebral blood flow are of paramount importance to be investigated. We studied cerebral circulation and oxygenation in a model of severe AS and compared it with a pharmacologically induced arterial hypotension of similar magnitude. Anaphylactic shock was induced by 1 mg intravenous ovalbumin (OVA) in sensitized rats. Rats were randomized to three groups: (i) no resuscitation (OVA; n = 10) (ii) intravenous volume expansion (10 mL in 10 min after OVA injection) (OVA + VE; n = 10); (iii) control hypotension (100 µg of nicardipine followed by continuous infusion of 1 mg · 100 g · h intravenously; NICAR; n = 10). Mean arterial pressure (MAP), carotid blood flow (CBF), cardiac output, cerebral cortical blood flow (CCBF; estimated by laser Doppler technique), and cerebral tissue oxygen pressure (PtiO2) were recorded over the 15 min following AS induction in all three groups. Results are expressed as mean (SD). One minute after OVA or nicardipine injection, there was a rapid and significant 50% decrease in MAP from basal values. In the OVA group, AS severely altered systemic and cerebral hemodynamics in 5 min: 93% (SD, 4%) decrease in CBF, 66% (SD, 8%) in CCBF, and 44% (SD, 8%) in PtiO2; the decrease in CBF was significantly (P < 0.05) attenuated in the OVA + VE group; however, CCBF and PtiO2 were not statistically different in the OVA versus OVA + VE groups. On the contrary, nicardipine-induced hypotension had only a limited impact on CBF, cardiac output, CCBF, and PtiO2 for a similar MAP decrease. There was a linear relation between CCBF and blood pressure in the OVA (regression slope: 0.87 [SD, 0.06]; median r = 0.81) but not in the NICAR group (regression slope: 0.23 [SD, 0.32]; median r = 0.33). Anaphylactic shock resulted in severe impairment of cerebral blood flow and oxygenation, beyond what could be expected from the level of arterial hypotension.