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Two probable anaphylactic events during consecutive cranial surgeries: case report/Dos probables eventos de anafilaxia durante cirugias craneales consecutivas. Reporte de caso.


Anaphylaxis is a systemic life-threatening hypersensitivity reaction (HR). (1) Perioperative anaphylaxis is among the main causes of anesthetic complications, with an incidence rate of 1/1250 to 1/18,600 procedures and a mortality rate between 4% and 4.7% (pharmacological anaphylaxis). (2) It is caused by the stimulus of bioactive mediators releasing mast cells and basophils, in 2 or more body systems, resulting in increased capillary permeability, vasodilatation, bronchoconstriction, and hypotension. (3)

Intraoperative anaphylaxis is a complex diagnosis as several symptoms cannot be evaluated in a sedated or unconscious patient, the cutaneous signs are hidden under the surgical drapes, and several drugs are administered simultaneously. (3,4) A total of 90% of the cases develop during induction, although there are late reactions as well, and the symptoms exhibit varying intensities, ranging from mild HRs with a preponderance of cutaneous manifestations (grade I) to cardiac and/or respiratory arrest (grade IV). (3,5,6) In thepresenceofonly1 symptom, intraoperative anaphylaxis may be misdiagnosed, in addition to the lack of an evaluation by the allergy clinic, and the risk of a new--potentially lethal--exposure to the agent involved. (6)

The most frequent signs in the presence of adverse reactions are the absence of pulse, difficult ventilation from bronchospasm, desaturation, and even cardiovascular collapse or cardiac arrest as the primary manifestation. (3,5) The reduction in end-tidal C[O.sub.2] (ETC[O.sub.2]) below 20 mm Hg has also been considered a valuable marker. (6,7)

Patient information

A 44-year-old male patient from a rural area, admitted to the intermediate care unit following his discharge from the intensive care unit (ICU), as a result of supraventricular tachycardia (SVT) over an elective cranial surgery which led to the interruption of the procedure (Table 1). A mild right hemiparesis was identified in the patient on clinical examination. The cardiology evaluation failed to identify any alteration and concluded that the SVT was the result of surgical manipulation or autonomic reflex. An amount of 10 mg of propanolol b.i.d. were prescribed, with a Goldman 2 index classification. No allergies (neither food nor drugs) were reported during the anesthetic evaluation and the patient was classified as American Society of Anesthesiologists (ASA) class 2 and was rescheduled.

Clinical findings

The patient was admitted to the OR with normal vital signs and 95 kg of body weight. Balanced anesthesia was administered for induction (Tables 1 and 2) and endotracheal intubation was performed with a No. 8.5 endotracheal intubation tube (ETT). The surgical procedure began with a 99% oxygen saturation ([SpO.sub.2]) and 30mm Hg of ETC[O.sub.2]. Vital signs were normal during maintenance. One hour after induction, suddenly and with no previous blood pressure (hypotension) or heart rate (bradycardia) alterations, sustained and progressive declines in ETC[O.sub.2] and [SpO.sub.2] (down to 24mm Hg and 92%, respectively) were recorded.

Diagnostic evaluation

Due to the alterations in ETC[O.sub.2] and [SpO.sub.2], malfunction of the ETT device was ruled out initially. Immediately after, the absence of palpable pulse and SVT was identified in the multiparameter monitor, with signs of pulseless electrical activity (PEA). Furthermore, when removing the surgical drapes, generalized edema was evidenced and consequently the patient was diagnosed with probable grade IV anaphylaxis.

Therapeutic intervention

Advanced cardiopulmonary resuscitation (CPR) was initiated with continuous chest compressions, IV administration of 1mg of adrenalin and manual ventilation. Two minutes later, return of spontaneous circulation (ROSC) developed and the compressions were discontinued. However, they had to be reinitiated 1 minute later because of ventricular fibrillation (VF) requiring a 200 joules biphasic shock. A second dose of adrenaline was administered. The VF relapsed on 3 occasions and the same treatment was repeated. After 2 minutes, ROSC was confirmed and a subclavian venous catheter and a radial arterial catheter were placed.

Follow-up and results

The patient was admitted to the postanesthesia care unit with 70/50 mm Hg of invasive arterial pressure, 130 bpm, 90% [SpO.sub.2], central venous pressure of 10 cm[H.sub.2]O, under volume controlled mechanical ventilation and dopamine at adjustable dose. 250 mg of hydrocortisone t.i.d. were administered 10 hours after PEA, and the patient was extubated without any complications with a Glasgow score of 14 points, 15 hours later. The patient was then transferred to the intermediate care unit where dopamine was then withdrawn after 3 days and 6 days later was transferred to the general hospitalization floor from where he was finally discharged.


The intermediate care unit evaluation focused on the SVT that led to the interruption of surgery because of an initial suspicion of cardiac pathology. However, the medical record indicated that the patient was admitted to the ICU following distributive shock resulting from anaphylaxis secondary to an adverse drug reaction (ADR), with hypotension and generalized erythema. Consequently, this first event was probably consistent with grade III anaphylaxis.

The primary cause of perioperative HRs is neuromuscular relaxants (NMRs) (50% to 70%), followed by latex (12% to 16.7%), and antibiotics (15%). (2,6) Reviewing the role of the various drugs administered over surgery in the case of immediate HRs (Table 2), sodium thiopental is often involved (incidence 1:30,000), although propofol may also be the culprit. Midazolam (administered in 2 surgeries) and fentanyl (administered in all of them) rarely trigger these reactions. (8)

Two steroid monoquaternary compounds were used (Rocuronium and Vecuronium), with replaced ammonia ions. These ions represent allergenic sites involved in the specific immunoglobulin E (IgE) recognition which could explain the crossed reactivity (CR) in skin tests of 60% to 70% of patients allergic to NMRs. CR to all relaxants is more frequent when a steroid compound triggered the initial reaction. There were also HRs in NMRs-naive patients because there is CR with cosmetics, foods, and disinfectants. (9)

Other late intraoperative anaphylaxis-causing agents are iodine povidone and chlorhexidine. (10) In a previous report (11) Naranjo's algorithm was used to assess the causality of an ADR. This algorithm enabled the analysis of a second HR, with a score of 5 for the relaxant and povidone, which makes them potential ADR agents. (12) Considering that few cases were reported in response to topical povidone, the NMR would then be the causal agent. (13)

Investigating the cause of anaphylaxis may be complex, since there may be several agents involved. (8) 3 necessary evidences have been described: medical record, biological evaluation, and skin tests. (14) The biological evaluation identifies the presence of an allergic mechanism in the reaction through early laboratory tests (total tryptase blood test and plasma histamine) and late laboratory tests (prick test, basophil activation, challenge tests, and specific IgE immunoassays). (1,3,5,8,14) In this 2 potential anaphylactic events, only clinical evidence was available. Moreover, the availability of the other tests required in our setting at the time of presentation is unclear.

The critical situation was neglecting the first HR since the patient should have been evaluated by the allergy clinic and the procedure rescheduled, once the agent involved was identified. Failure to do so led to a new exposure to the agent, resulting in a more severe preventable reaction. (6,15) Actually, every perioperative reaction must be investigated to ensure safe anesthetic procedures in the future, because even a mild reaction may be due to hypersensitivity and hence be neglected or attributed to unspecificreactions. (8,16,17)

Some therapeutic approaches to these potential HRs may be optimized; for instance, administering IV fluid challenges, Chlorphenamine and Amiodarone (to avoid the relapse of atrial fibrillation) (1,18) (Table 3). The value of the acronym dislodgement, obstruction, suspected pneumothorax and equipment or operator problem (DOPE) has been recognized to address the deterioration of the patient in mechanical ventilation. (20)

Following a HR, the anesthesiologist shall request laboratory tests that contribute to a clinical diagnosis, in addition to interconsulting with the allergy clinic to investigate the causal agent. Furthermore, all the Peruvian anesthesiology services nowadays have a mandatory record of adverse events. Finally, the early identification of the disruption in ETC[O.sub.2] y [SaO.sub.2] enabled the introduction of timely CPR measures to avoid a fatal outcome.

Patient's opinion

There were no follow-up anesthesia visits to give the patient a detailed written pharmacological report, and the result of the patient's allergy evaluation is unknown.

Informed consent

The Hospital Ethics Committee approved the publication of this case report because the patient is not a resident of the hospital jurisdiction to be able to obtain a written consent.

Ethical responsibilities

Protection of persons and animals: The authors declare that the procedures followed were consistent with the ethical standards of the responsible human experimentation committee and pursuant to World Medical Association and the Declaration of Helsinki.

Confidentiality of the information: The authors state that they have followed the institutional protocols regarding the publication of patient information.

Right to privacy and informed consent: The authors have obtained the informed consents of the patients and/or individuals mentioned herein. The custodian of this document is the corresponding author.


The authors did not receive any financial contributions for this article.

Conflicts of interest

The authors have no conflict of interest to disclose.


(1.) Chapman J, Lalkhen AG. Anaphylaxis. Anaesth Intensive Care Med 2017;18:16-21.

(2.) Mertes PM, Volcheck GW, Garvey LH, et al. Epidemiology of perioperative anaphylaxis. Presse Med 2016;45:758-767.

(3.) Kannan JA, Bernstein JA. Perioperative anaphylaxis: diagnosis, evaluation and management. Immunol Allergy Clin North Am 2015;35:321-334.

(4.) Peroni DG, Sansotta N, Bernardini R, et al. Perioperative allergy: clinical manifestations. Int J Immunopathol Pharmacol 2011;24 (3 suppl):S69-S74.

(5.) Moneret-Vautrin DA, Mertes PM. Anaphylaxis to general anesthetics. Chem Immunol Allergy 2010;95:180-189.

(6.) Mertes PM, Tajima K, Regnier-Kimmoun MA, et al. Perioperative anaphylaxis. Med Clin N Am 2010;94:761-789.

(7.) Gouel-Cheron A, de Cahisemartin L, Jonsson F, et al. Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions. Br J Anaesth 2017;119:908-917.

(8.) Volcheck GW, Mertes PM. Local and general anesthetics immediate hypersensitivity reactions. Immunol Allergy Clin North Am 2014;34:525-546.

(9.) Naguib M, Lien CA, Meistelman C. Miller RD. Pharmacology of neuromuscular blocking drugs. Miller's anesthesia 8th ed. Elsevier, Canada:2015.

(10.) Ewan PW, Dugue P, Mirakian R, et al. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin Exp Allergy 2010;40:15-31.

(11.) Aguilera-Castro F. Intraoperative recurrence of probable allergic reaction to remifentanil. Case report. Rev Colomb Anestesiol 2017;45 (s1):31-35.

(12.) Holloway K, Green T. Comites de Farmacoterapia. Guia Practica. OMS. Departamento de Medicamentos Esenciales y Politica Farmaceutica, Francia:2003.

(13.) Caimmi S, Caimmi D, Cardinale F, et al. Perioperative allergy: uncommon agents. Int J Immunopathol Pharmacol 2011;24 (3 suppl):S61-S68.

(14.) Dewachter P, Mouton-Faivre C, Emala CW. Anaphylaxis and anesthesia: controversies and new insights. Anesthesiology 2009;111:1141-1150.

(15.) Pedersen AF, Green S, Rose MA. Failure to investigate anaesthetic anaphylaxis resulting in a preventable second anaphylactic reaction. Anaesth Intensive Care 2012;40:1053-1055.

(16.) Berroa F, Lafuente A, Javaloyes G, et al. The incidence of perioperative hypersensitivity reactions: a single-center, prospective, cohort study. Anesth Analg 2015;121:117-123.

(17.) Bevilacqua-Alen E, Illodo-Miramontes G, Lopez-Gonzalez JM, et al. Anesthetic management of muscle relaxant allergy. Rev Argent Anestesiol 2017;75:7-12.

(18.) Callaway CW, Soar J, Aibiki M, et al. Part 4: advanced life support: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2015;132 (16 suppl 1):S84-S145.

(19.) McEvoy MD, Thies KC, Einav S, et al. Cardiac arrest in the operating room: Part 2-Special situations in the perioperative period. Anesth Analg 2018;126:889-903.

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Rafael Ramirez-Gonzales (a), Roman Augusto Del-Castillo-Gervasi (a), Carlos Javier Shiraishi-Zapata (b), John Neper Laurencio-Ambrosio (a)

(a) Department of Anesthesiology and Surgical Center, Hospital Maria Auxiliadora, Ministry of Health, Lima, Peru

(b) Surgical Center and Anesthesiology Service, Hospital EsSalud, Talara, Peru.

How to cite this article: Ramirez-Gonzales R, Del-Castillo-Gervasi RA, Shiraishi-Zapata CJ, Laurencio-Ambrosio JN. Two probable anaphylactic events during consecutive cranial surgeries: case report. Colombian Journal of Anesthesiology. 2018;46:322-326.

Read the Spanish version of this article at:

Correspondence: Servicio de Centro Quirurgico y Anestesiologia, Hospital EsSalud, Avenida Panamericana s/n Parinas, Talara, Peru. E-mail:
Table 1. Timeline.

Date                  Surgical and medical therapy events

02/19/2007            Emergency surgery: DC to remove
                      the acute subdural hematoma
                      secondary to severe TBI. Position:
                      ventral decubitus. Balanced
                      general anesthesia. Monitoring:
                      noninvasive blood pressure,
                      electrocardiography (3 bipolar
                      electrodes), capnography and pulse
11/7/2007             1st elective surgery: CP with
                      autologous cranial bone flap.
                      Position: dorsal decubitus.
                      Balanced general anesthesia. The
                      same monitoring
11/8/2007-11/12/2007  IMCU admission
                      evaluation. Surgery rescheduled
11/22/2007            2nd elective programing: DC with
                      autologous cranial bone flap.
                      Position: dorsal decubitus.
                      Balanced general anesthesia. The
                      same monitoring

Date                  Adverse reaction     Management

02/19/2007            None                 ICU monitoring

11/7/2007             SVT                  Surgery was interrupted.
                                           The patient was
                                           cardioverted in the OR and
                                           admitted to the ICU

11/8/2007-11/12/2007  None                 Cardiology and anesthesia

11/22/2007            PEA due to probable  Advanced CPR. PACU management
                      anaphylaxis          during the immediate
                                           postoperative period

CP=cranioplasty, CPR=cardiopulmonary resuscitation, DC = decompressive
craniotomy, ICU=intensive care unit, IMCU=intermediate care unit,
PACU= postanesthesia care unit, PEA=pulseless electrical activity,
SVT = supraventricular tachycardia, TBI=traumatic brain injury.

Source: Authors.

Table 2. Detailed list of drugs used in the 3 surgical procedures.

Date        Surgical procedure    Preinduction medication

02/19/2007  Emergency DC          5mg of Midazolam and 8
                                  mg of Dexamethasone

11/07/2007  1st elective CP       8mg of Dexamethasone,
            (interrupted because  10mg of
            of SVT)               Metoclopramide, 5 mg of
11/22/2007  2nd elective CP       80 mg of Lidocaine
            (PEA event)

Operative asepsis: iodine povidone in the 3 surgeries

Date        Induction

02/19/2007  Fentanyl 200 [micro]g and
            Vecuronium 8 mg

11/07/2007  160 mg of propofol, 250 [micro]g
            of fentanyl, 70 mg of

11/22/2007  Fentanyl 250 [micro]g, 400mg of
            sodium thiopental and
            8 mg of Vecuronium

Operative asepsis: iodine povidone in the 3 surgeries

Date        Maintenance

02/19/2007  Sevoflurane 100% 2.5% to
            2% in 2L of [O.sub.2] at 100%.
            Two additional doses of
            100 [micro]g of fentanyl
11/07/2007  Sevoflurane 100% 2.5% in
            21 of [O.sub.2] at 100%

11/22/2007  Sevoflurane 100% 2.5% in
            2 L of [O.sub.2] at 100%.
            Additional doses: 50 [micro]g
            of fentanyl and 2 mg of

Operative asepsis: iodine povidone in the 3 surgeries

CP=cranioplasty, DC = decompressive craniotomy, PEA=pulseless
electrical activity, SVT = supraventricular tachycardia.

Source: Authors.

Table 3. Differential diagnosis and management of perioperative
anaphylaxis in the adult.

Differential diagnosis  Management of severe anaphylaxis

Always keep in mind
Bronchial asthma        Airway (A), breathing (B), circulation (C),
                        disability (D), and exposure (E)
Cardiac arrhythmia      Ask for help
Myocardial infarction   Position the patient on a flat surface
Pericardial tamponade   Raise the patient's legs
Pulmonary edema         Evaluate any life-threatening issues for the
                        patient: airway (laryngeal
Pulmonary embolism      edema, hoarseness, stridor), breathing
                        (dyspnea, tachypnea, wheezing,
Tension pneumothorax    fatigue, cyanosis, [SpO.sub.2] <92%),
                        circulation (paleness, cold and humid
Venous embolism         skin, hypotension, lipothymia)
Sepsis                  Assess mental health disorders: confusion,
                        somnolence, comma
Hereditary angioedema   Pre-cardiac arrest management
Mastocytosis            Discontinue or remove the causal agent
                        (relaxants, antibiotics, blood
Drug overdose           products, contrast media or latex). Stop the
                        surgical procedure if
Malignant hyperthermia
(secondary to           possible.
succinylcholine)        In the presence of respiratory distress,
                        intubate immediately; use [FIO.sub.2]
Myotonia and masseter
spasm (secondary
to                      100%. If sever bronchospasm develops, monitor
succinylcholine)        Repeated doses of adrenaline (100-300
                        [micro]g) every 5 minutes and
(secondary to           increase the dose if no improvement is
                        identified (in the absence of an
succinylcholine)        IV line, 300-500 [micro]g IM) (+ or -) 2 UI of
                        IV Vasopressin
                        Start the adrenalin infusion (0.05-0.3
                        [micro]g/kg/minute IV) for maintaining
                        a SBP [greater than or equal to] 90 mm Hg
                        under constant monitoring (check for myocardial
                        Vasopressin or norepinephrine infusion in
                        cases of hypotension
                        refractory to a dose of >2mg of adrenalin
                        IV fluid challenge, IV access using a large
                        catheter: 500-1000 mL (20
                        mL/kg) of crystalloid. Discontinue the colloid
                        infusion when this could
                        be the causal agent
                        H1 blockers: 50 mg of diphenhydramine, 10 mg
                        of chlorphenamine
                        H2 blockers: 20 mg of famotidine IV
                        Corticosteroid: 50-200 mg of hydrocortisone or
                        1-2 mg/kg of
Cardiac arrest
                        Start CPR in the absence of carotid pulse in
                        Adrenalin 100-1000 [micro]g IV; you may repeat
                        the dose administration
                        every 3-5 minutes, or replace for a dose of
                        40U of IV vasopressin
                        Briefly disconnect the ventilator if auto-PEEP
                        is suspected
                        Administer H1 and H2 blockers and steroids at
                        the above-mentioned doses
                        Consider extracorporeal support in patients
                        with good CPR without ROSC

CPR=cardiopulmonary resuscitation, [FIO.sub.2]=fraction of inspired
oxygen, PEEP=positive end-expiratory pressure, ROSC=return of
spontaneous circulation. Adapted from Chapman and Lalkhen, (1)
Mertes et al, (6) and McEvoy et al. (19)

Source: Authors.
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Title Annotation:CASE REPORT
Author:Ramirez-Gonzales, Rafael; Del-Castillo-Gervasi, Roman Augusto; Shiraishi-Zapata, Carlos Javier; Laur
Publication:Revista Colombiana de Anestesiologia
Date:Oct 1, 2018
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