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Background The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system. Methods Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD. Results Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001). Conclusions During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.

Background Epinephrine and more recently arginine vasopressin (AVP) alone or in combination have been proposed in patients with anaphylactic shock, but few experimental data exist. The authors investigated the effects of epinephrine only, AVP only, or epinephrine followed by AVP in a model of anaphylactic shock. Methods Ovalbumin-sensitized Brown Norway rats were anesthetized, intubated, and shock induced with ovalbumin. Rats (n = 6/group) were randomly allocated to receive 5 min after shock onset: (1) saline (no-treatment group); (2) two boluses of epinephrine followed by continuous infusion (epinephrine group); (3) AVP bolus followed by continuous infusion (AVP group); (4) epinephrine bolus followed by AVP continuous infusion (epinephrine + AVP group). Mean arterial pressure (MAP) and skeletal muscle oxygen pressure (PtiO2) were measured. Continuous infusion rates were titrated to reach MAP values of 60 mmHg. Survival was analyzed. Results Without treatment, MAP and PtiO2 decreased rapidly with 0% survival. In the epinephrine group, MAP and PtiO2 recovered after an initial decrease, with 84% survival. In the AVP group, MAP was partially restored and subsequently decreased; PtiO2 values decreased to values similar to those in the no-treatment group; survival was 0%. In the epinephrine + AVP group, MAP and PtiO2 values increased more slowly as compared with the epinephrine group; survival was 100%. Conclusions In this model of anaphylactic shock, early treatment with epinephrine followed by continuous epinephrine or vasopressin infusion resulted in an excellent survival rate, whereas vasopressin only resulted in a 100% death rate. These experimental results suggest that epinephrine must still be considered as the first-line drug to treat anaphylactic shock.

Background Arginine vasopressin (AVP) and terlipressin were proposed as alternatives to catecholamines in shock states characterized by decreased plasma AVP concentrations. The endogenous plasma AVP profile in anaphylactic shock is unknown. In an ovalbumin-sensitized anesthetized anaphylactic shock rat model, the authors investigated (1) plasma AVP concentrations and (2) the dose versus mean arterial pressure response for exogenous AVP and terlipressin and compared them with those of epinephrine. Methods In a first series of rats (n = 12), endogenous plasma AVP concentrations were compared with a model of pharmacologically induced hypotension (nicardipine, n = 12). A second series was randomly assigned to three groups (AVP, n = 7; terlipressin, n = 7; epinephrine, n = 7) and dose (AVP: 8 doses, 0.03-100 U/kg; terlipressin: 7 doses, 0.03-30 microg/kg; epinephrine: 7 doses, 0.3-300 microg/kg)-response mean arterial pressure curves were plotted. Data are expressed as mean +/- SD. Results Endogenous plasma AVP concentrations were significantly lower in anaphylactic shock (57 +/- 26 pg/ml) than in the nicardipine group (91 +/- 43 pg/ml; P < 0.05). The ED50 was 10.6 microg/kg (95% confidence interval, 7.1-15.9) for epinephrine and 4.1 U/kg (95% confidence interval, 3.0-5.6) for AVP. Terlipressin did not change mean arterial pressure, regardless of the dose used. Conclusions In a rat model, anaphylactic shock is associated with inadequately low plasma AVP concentrations. For clinically relevant doses, AVP and epinephrine had comparable effects on mean arterial pressure and heart rate values, whereas, unexpectedly, terlipressin was ineffective. These results are consistent with reports in humans experiencing anaphylaxis where AVP injection restored arterial pressure.

Background The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known. Methods Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. Results In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05). Conclusions This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.

This article has been selected for the ANESTHESIOLOGY CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue.

The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known.Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes.In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P0.05).This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.