it has been reported that serious problems during general anesthesia occur in 0.4% of patients .
it may be difficult to detect anaphylactic reactions during anesthesia because various medications are administered in short periods of time , and transient interactions between drugs may take place .
there have been many reports on anaphylactic reactions due to propofol or muscle relaxants during anesthesia induction .
in contrast , cases on anaphylactic reactions before induction are rare , but in the absence of adequate monitoring and immediate treatment , can be fatal to the patients .
we report life - threatening conditions in a patient due to a severe anaphylactic reaction during transfer to the operating room before induction of anesthesia .
an 84-year - old woman , 148 cm in height and 61 kg in weight was scheduled for open reduction and internal fixation due to left calcaneous fracture with dislocation .
she had been taking hypertension medication for five years but had no previous history of asthma , allergic rhinitis , or atopic dermatitis .
however , one year ago she was treated with conservative management after experiencing dizziness and general weakness following injection of an unknown drug .
she received no premedication other than tridol , which was administered for pain control a day before the surgery .
her blood pressure , heart rate , and temperature were 130/80 mmhg , 68 beat / min , 36.8c , respectively .
after a negative intradermal skin test ( 2 mg / ml in normal saline with cefbuperazone ( tomiporan ) , 1 g of cefbuperazone ( tomiporan ) was injected before transfer to the operating room .
fifteen minutes later in the surgical waiting room , the patient had slight difficulty in breathing but had an alert mental state .
five minutes later , as the patient was being moved to the operation bed , the patient became incontinent of urine and unconsciousness .
her blood pressure was 105/65 mmhg , heart rate 62 beat / min , and arterial oxygen saturation 75% . intubation was performed immediately without using muscle relaxants .
on auscultation , wheezing was apparent in both lungs and airway pressure increased to 30 cmh2o after the ventilator was applied .
sudden , profound hypotension ( blood pressure 62/43 mmhg ) and bradycardia ( heart rate 45 beat / min ) developed .
the patient was promptly loaded with fluid along with two doses of ephedrine 20 mg .
her blood pressure rose to 85/54 mmhg and then dropped to 50/22 mmhg a minute later .
a central line was placed in the right internal jugular vein and an arterial cannula was inserted into the right femoral artery .
arterial blood gas values were fio2 1.0 , ph 7.288 , po2 355 mmhg , be 6.1 meq , and arterial oxygen saturation 98.3% .
since the patient received no special medications other than the intravenous antibiotic injection before arriving at the operation room , a clinical diagnosis of anaphylactic reaction was made and methyl prednisolone ( solumedrol ) 500 mg was intravenously injected .
three doses of epinephrine 20 g were administered but there was no response : blood pressure 60/36 mmhg , heart rate 113 beat / min , and blood pressure 49/37 mmhg , heart rate 130 beat / min .
after three additional doses of 200 g of epinephrine were administered , the patient s blood pressure and heart rate were then maintained at 110130/5060 mmhg and 80100 beat / min , respectively .
forty minutes after resuscitation , her blood pressure was maintained at around 120/60 mmhg with epinephrine infusion and the patient was transferred to the intensive care unit where a mechanical ventilator was applied . after an hour at the intensive care unit ,
arterial blood gas values were fio2 1.0 , ph 7.256 , po2 346 mmhg , pco2 49.7 mmhg , be 5.5 meq , and arterial oxygen saturation 99.7% .
after two hours in the intensive care unit , arterial blood gas value normalized : fio2 0.3 , ph 7.345 , po2 87.5 mmhg , pco2 42.3 mmhg , be 5.8 meq , and arterial oxygen saturation 97.1% .
after three hours in intensive care unit , the patient s was alert , her mean arterial blood pressure was > 80 mmhg , and she showed no signs of airway obstruction or wheezing on auscultation .
five hours later , the patient was transferred to the general ward and surgery was postponed .
eight weeks later , a skin prick test confirmed a positive reaction ( wheal 4  3.5 , flare 7  6 mm ) to cefbuperazone ( tomiporan ) .
anaphylactic reaction is an immediate life - threatening reaction mediated by ige and propagated by mediators such as histamine , tryptase , leukotrienes , platelet activating factor , nitric oxide , inflammatory prostaglandins , and bradykinin .
it can lead to intravascular volume depletion , myocardial suppression and increased airway resistance , that results in sudden severe hypotension , hypoxemia , tissue hypoxia , and acidosis .
the most common causes that trigger generalized reaction during anesthesia are neuromuscular blocking agents , latex , and antibiotics , with antibiotics reported as the cause in 1015% of all cases .
-lactam antibiotics , such as penicillin , cephalosporin , carbapenem , and monobactam antibiotics , are involved in generalized reactions in 80% of these cases .
however , recent wide spread use of cephalosporin antibiotics during perioperative period to prevent infections has led to an increase in the incidence of drug reactions due to cephalosporin antibiotics .
cephalosporins are semi - synthetic antibiotics , derivatives of cephalosporin acremonium , and are composed of a -lactam ring connected to a 6-member dihydrothiazine ring .
cephalosporin exerts its antibacterial effect by disrupting synthesis of the peptidoglycan layer in bacterial cell wall .
this drug has broad spectrum activity and is administered as a first - line prophylactic drug to prevent infections in surgical procedures .
generally , the first generation cephalosporins work more effectively on gram positive bacteria and have less activity on gram negative bacteria . with few exceptions ,
the most common side effects of cephalosporins are skin reactions such as maculopapular exanthema and urticaria , which are reported to occur in 13% of patients .
only 0.00010.1% of the side effects is anaphylactic reaction , which is thus very rare . according to fisher et al . , the most common clinical feature of anaphylactic reaction is cardiovascular collapse , occurring in their study in 389 out of 442 people , along with bronchospasm occurring in 161 people , of which 72 have having asthmatic bronchospasm . among cutaneous signs ,
there were 201 people with erythema , 55 with rash , and 37 with urticaria .
in accordance with these statistics , our patient showed all the important clinical features such as cardiovascular collapse , asthmatic bronchospasm , and erythematous rash .
furthermore , in patients with severe reactions , the first clinical features were a fall in blood pressure in 122 people , difficulty to inflate in 115 , flush in 94 , coughing in 28 , rash in 20 , desaturation in 15 , and cyanosis is 12 out of 440 people . in our case ,
the patient had difficulty in inflating with wheezing immediately on arrival to the operation room , and considering the normal range of blood pressure with signs of bradycardia and oxygen desaturation ( 78% ) , difficulty in inflation was the first clinical feature . while it has been reported that anaphylactic reactions occur most commonly after the age of 40 in women and 50 in men , only 0.4% of all anaphylactic reactions occur in over 80 years of age .
therefore , the severe anaphylactic reaction noted in our 84-year - old patient is very unusual . according to laxenaire et al . , grade iii life - threatening reactions including cardiovascular collapse , tachycardia or bradycardia , arrhythmia , and severe bronchospasm occurred in 62.6% of the patients in their study .
bronchospasm only occurred in 21.3% of grade ii reactions , whereas 75.4% of the patients with grade iii reactions had bronchospasm .
, it took 20 minutes for the symptoms to occur after antibiotic injection in the ward , which is still unlike most immediate reactions in which symptoms start to manifest promptly .
initiative resuscitation with ephedrine and phenylephrine failed to restore the patient s blood pressure but epinephrine was effective .
the normalization of blood pressure can be explained by a decrease in allergic reaction due to -2 agonists along with an increase in blood pressure to the effects of epinephrine .
anaphylactic reactions that occur during induction or anesthesia can be treated immediately . however , if airway obstruction and severe hypotension occur during transfer , as in this case , they can be fatal .
if anaphylaxis occurs during anesthesia , several causative agents can be considered : myocardial infarction , drug overdose , pulmonary embolus , irritant - induced bronchospasm , endotracheal tube malfunction , aspiration , hypoglycemia , and stroke . however , our patient had no premedication before transferring to the operating room other than the antibiotics injection .
thus , we were able to make a fast diagnosis of anaphylactic reaction due to antibiotics .
our patient was injected with antibiotics after a negative skin test with 2 mg / ml in normal saline concentration . according to romano , 2 mg / ml in normal saline concentration
is nonirritant in a control group but very sensitive in subjects that have immediate reactions to cephalosporin .
today , the highest concentration accepted for prick and intradermal testing in europe is 2 mg / ml for cephalosporins . on the other hand ,
other studies have used normal saline concentrations in the range of 0.5250 mg / ml for hypersensitivity diagnosis .
this is less than the amount used in our case but the possibility of a false negative result can not be eliminated because the test volume was too small [ 1315 ] .
one limitation of this study is that there was no ige test result to corroborate the clinical findings that the patient had undergone an anaphylactic reaction .
also , considering her clinical features , course of treatment , and the positive skin prick test , a diagnosis of anaphylactic reaction due to cephalosporin should still be made .
however , as demonstrated in the present case , if they occur 2030 minutes after injection , they can take place during transfer from the ward to the operating room .
therefore , careful observation and monitoring is required when patients are being transferred after a prophylactic antibiotics injection .
 although uncommon , anaphylactic reactions during surgery are very dangerous and can result in serious morbidity . 
 various anesthetics can trigger anaphylactic reactions , and incidents with cephalosporin antibiotics are on the rise . in the case 
 presented , an 84-year - old woman scheduled for calcaneus fracture surgery , was injected with cefbuperazone as a prophylactic antibiotic . on the way to the operating room , 
 before induction of anesthesia , the patient lost consciousness and showed signs of hypoxemia , and anaphylactic reaction , which included hypotension , bronchospasm , and rash . 
 five hours after immediate intubation and fluid resuscitation , the patient was extubated and transferred to the general ward . 
 eight weeks later , the skin prick test confirmed a positive reaction to cefbuperazone . 
INTRODUCTION
CASE REPORT
DISCUSSION