Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective

Abstract

There is no standardized method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2× baseline tryptase+2 mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). To validate consensus equation in a perioperative setting analyses of cases of suspected perioperative anaphylaxis during general anaesthesia (GA) were performed. Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced. A total of 82 patients (60 females, mean age 56.5 years±SD17.2) underwent investigation. Sixty (73%) patients fulfilled WAO criteria for anaphylaxis, and 22 patients did not. Aetiology included 59% IgE-mediated anaphylaxis, 2% non-IgE-mediated anaphylaxis, 12% anaphylaxis of unknown cause and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included the following: NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71 of 82 (87%) patients (60 anaphylaxis and 11 controls). The median interquartile range (IQR) time from reaction to peak MCT was 1.34 (0.82-2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98% and 44%, respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=.0001). This equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.

Paired acute‐baseline serum tryptase levels in perioperative anaphylaxis: An observational study

“…Indeed, MC activation has been reported in atherosclerosis‐related cardiovascular events, coagulation abnormalities, and response to infectious agents . In line with previous cohorts, our results confirm that the consensus algorithm sAT >([1.2 × sBT] + 2) μg/L is a good compromise between empirical thresholds such as >(1.35 × sBT), which privileged sensitivity as high as 0.91 in previous literature and 0.81 in our study, or (sBT + 3) μg/L, which resulted in sensitivity values as low as 0.63 in the literature and 0.72 in our hands. It achieves a good performance level even in patients whose sAT does not exceed 11.4 μg/L.…”

“…Other decision thresholds for total tryptase variation during MC degranulation have been proposed, including sAT being >(1.35 × sBT), >(1.2 × sBT), >(3 + sBT) μg/L, >11.4 μg/L (the manufacturer's upper limit of reference values for sBT,), or >14 μg/L . Yet, serial tryptase determination is seldom implemented and a common decision threshold has not been adopted in daily practice …”

Specialist perioperative allergy clinic services in the UK 2018: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6) investigation of perioperative anaphylaxis

“…Case series have demonstrated that the Dynamic Tryptase algorithm can detect possible release more sensitively than thresholds . In NAP6, DT assessments increased detection of acute release and should be used when the Tp is within the reference range.…”

“…Tryptase levels plateau between 30 and 90 minutes post‐reaction Dynamic tryptase results may identify tryptase release in more cases than exceeding fixed thresholds of 11.4 or 14 μg/L Exposure to opioids such as pholcodine may correlate with neuromuscular blocking agent (NMBA) anaphylaxis.…”

Hypersensitivity Reactions During Anaesthesia Care: An 11-Year Experience From A Tertiary Hospital

“…Determination of mast cell Tryptase can be useful in the discrimination of IgE and non-IgE-mediated reactions [18]. The presence of this enzyme is therefore a key element in diagnosing anaphylactic reactions [19].…”