Angioedema related to angiotensin-converting enzyme inhibitors

Angioedema is a disorder characterized by well-demarcated nonpitting edema involving the tongue, floor of the mouth, larynx, lips, and face. This condition can progress to upper airway obstruction and death. Angiotensin-converting enzyme inhibitors (ACEIs), relatively new antihypertensive agents, act by blocking the formation of angiotensin II, a potent vasoconstrictor and stimulator of aldosterone formation. ACEIs also retard the breakdown of bradykinin, a potent vasodilator, which may lead to the edema seen in nonhereditary angioedema. These ACEIs include enalapril, captopril, lisinopril, saralasin acetate, and a combination of ACEI with diuretics (for example, Capozide). From August 1987 to January 1989, we treated six patients with a nonhereditary form of angioedema related to ingestion of angiotensin-converting enzyme inhibitors. Symptoms developed in all patients within 12 hours after their initial dose of an ACEI. They presented with shortness of breath and dysphagia associated with tongue and floor of the mouth edema. Two of the six required intubation and monitoring in the surgical intensive care unit for 36 to 48 hours. Three required supportive treatment and observation in an intermediate care unit, and one received supportive care in the clinic and was discharged the same day. Specifically, treatment consisted of cessation of inciting agent, steroids, antihistamines, and epinephrine, if not otherwise contraindicated. Assays of C1 esterase inhibitor levels and C4 were normal in all six patients; this was important in order to rule out hereditary forms of angioedema. These cases will be discussed, including a review of the literature, methods of diagnosis, pathophysiology, and treatment of angioedema.     

Anesthetic management of patients with Melkersson Rosenthal syndrome

Melkersson Rosenthal Syndrome (MRS) is a rare disorder characterized by relapsing facial paralysis, persistent or recurrent orofacial edema, and lingua plicata. It may cause difficult airway, drug allergy, and angioedema. In our anesthetic management of two patients with MRS, preanesthetic immunological blood examination and skin tests for hypersensitivity to anesthetic drugs were applied. Because the principal goal is to avoid all factors that may stimulate, an allergic reaction, anesthetic drugs known to trigger urticaria were avoided. Body and operating room temperatures, changes of which may trigger allergic reactions, were kept constant during the perioperative period. Emergency precautions were taken for probable angioedema. MRS is a rare syndrome, and if its manifestations are misunderstood as simple facial paralysis, it may be overlooked by anesthesiologists. Anesthesiologists must be careful of several problems in patients with MRS.     

Acute upper airway angioedema secondary to acquired C1 esterase inhibitor deficiency: a case report

PURPOSE: Adverse reactions to local anesthetics are widely reported. We report a case of acute upper airway angioedema presumed to be due to the local anesthetic articaine, which was subsequently diagnosed as acquired C1 esterase inhibitor deficiency. CLINICAL FEATURES: A 54-yr-old woman presented with a history of progressive facial and periorbital edema 24 hr after receiving articaine local anesthetic for a dental procedure. She was in mild respiratory distress but was not stridorous. After inhalational induction with sevoflurane in the operating room, direct laryngoscopy revealed marked edema of supraglottic structures including epiglottis, uvula and aryepiglottic folds and the larynx was not visualized. The patient's trachea was intubated under direct laryngoscopy. Seventy-two hours later, the endotracheal tube was removed and she made an uneventful recovery. Initially, the angioedema was thought to be caused by a hypersensitivity reaction to articaine. Later investigations showed normal C3 complement level, very low C4 complement and C1 esterase inhibitor levels confirming a diagnosis of C1 esterase inhibitor deficiency. Subsequently, the patient was started on androgen therapy. Her C1 esterase inhibitor level normalized and she remained symptom free nine months after initial presentation. CONCLUSION: We report a case of acute upper airway angioedema secondary to C1 esterase inhibitor deficiency requiring emergency airway management. Anesthesiologists should consider C1 esterase inhibitor deficiency in the differential diagnosis of patients with airway edema and be familiar with the acute and prophylactic treatment of patients with this diagnosis.     

Predicting airway risk in angioedema: staging system based on presentation.

Angioedema is an immunologically mediated, anatomically limited, nonpitting edema that can lead to life-threatening airway obstruction. To predict the risk of airway compromise in angioedema, we retrospectively reviewed 93 episodes in 80 patients from 1985 to 1995. Intubation or tracheotomy was necessary in 9 (9.7%) cases. Angiotensin-converting enzyme inhibitor use in 36 cases (39%) was associated with intensive care unit (ICU) admission (P = 0.05). ICU stay correlated significantly with presentation with voice change, hoarseness, dyspnea, and rash (P < 0.05). Voice change, hoarseness, dyspnea, and stridor were present in patients requiring airway intervention (P < 0.05). On the basis of our data, we propose a staging system by which airway risk may be predicted from the anatomic site of presentation. Patients with facial rash, facial edema, lip edema (stage I), and soft palate edema (stage II) were treated as outpatients and on the hospital ward. Patients with lingual edema (stage III) usually required ICU admission. All patients with laryngeal edema (stage IV) were admitted to the ICU. Airway intervention was necessary in 7% of stage III patients and in 24% of stage IV cases. No deaths were caused by angioedema. Airway risk in angioedema may be predicted by anatomic site of presentation, allowing appropriate triage with preparation for airway intervention in selected cases.     

Predictors of airway intervention in angioedema of the head and neck.

OBJECTIVE: Records of patients presenting with angioedema of the head and neck were analyzed to determine clinical factors that predict the need for airway intervention. METHODS: A review of patients with angioedema of the head and neck over a 10-year period was conducted. Data were collected regarding demographics, cause of edema, and sites of involvement. A logistic regression model was used to ascertain whether any clinical variables were significant in predicting the need for airway intervention. RESULTS: Review of 138 charts with an admitting diagnosis of angioedema yielded 66 cases of angioedema of the head and neck in 48 patients. Twenty-three (34.8%) patients required airway intervention. Logistic regression identified increasing age and angioedema involving the oral cavity/oropharynx as predictors of airway intervention; involvement of other sites, cause, and sex were not predictive. CONCLUSION: Location of edema and patient age predict which patients with angioedema of the head and neck are likely to require airway intervention.     

Impossibility of intubation due to angioedema secondary to an angiotensin-converting enzyme inhibitor

Angioedema secondary to treatment of one year's duration with angiotensin converting enzyme inhibitor (ACEI) (lisinopril) in a 56-year-old man scheduled for elective cardiac surgery led unexpectedly to impossible intubation. Surgical access (tracheostomy) was required when airway control was threatened. We review the clinical course, etiology and treatment of angioedema secondary to ACEI therapy. This is a life threatening complication which, though rare, is becoming increasingly frequent with increased use of such drugs.     

Angioedema pós‐operatório induzido por inibidor da enzima conversora da angiotensina: relato de caso

Background and objectivesAngioedema is a potentially fatal condition that may occur at any time in the perioperative period. It may result from histamine release, hypersensitivity reaction to drugs, or be triggered by bradykinin, in non‐allergic reactions of hereditary or acquired etiology. The aim of this report is to report a case of angioedema in the early postoperative period in a patient on antihypertensive medication involving angiotensin‐converting enzyme inhibitors.Case reportA 67‐year‐old male, Afro‐descendant, hypertensive, and taken enalapril maleate underwent orthopedic shoulder surgery under general anesthesia combined with brachial plexus block. The procedure lasted 3 hours uneventfully. After discharge from the post‐anesthesia care unit, the patient presented with angioedema and severe airway impairment. Tracheal intubation was attempted but it was impossible due to edema affecting the lips, tongue, and oropharyngeal region Emergency cricothyroidotomy was performed. The onset of angioedema had no causal relationship with the administration of any medication; there were no cutaneous manifestations and also not response to therapy for hypersensitivity reaction to drugs, such as antihistamines, corticoid, and adrenaline. It was considered to be mediated by bradykinin, as the patient had already had two similar episodes and was on regular medication (enalapril). The evolution was satisfactory.ConclusionAngioedema is a potentially fatal condition when it affects the airway, and should be recognized by anesthesiologists and physicians working in the emergency departments.     

Angioedema and angiotensin-converting enzyme inhibitors: are demographics a risk?

OBJECTIVES: The use of angiotensin-converting enzyme inhibitors (ACEI) has become the leading cause of acquired angioedema. Previous studies have suggested that certain patient populations may be at a higher risk for ACEI-induced angioedema. The objective of this study was to evaluate any demographic associations. STUDY DESIGN: A retrospective chart review. MATERIALS AND METHODS: Angioedema patients from 1999 to 2004 treated at a tertiary care hospital were reviewed. Demographics, inciting factors, and comorbid conditions were examined. RESULTS: One hundred eighty-two patients met inclusion criteria. Sixty-three percent of patients with angioedema had ACEI triggers. Eighty-one percent of all ACEI angioedema occurred in black patients. Of all angioedema patients, 70% (95% confidence interval [CI], 62%-78%) of black patients noted an ACEI as the inciting agent compared with 44% (95% CI, 30%-59%) in other patient groups. Black patients were 3.03 times more likely to have angioedema from an ACEI than all other patient groups (95% CI, 1.54-5.94). CONCLUSION: This study represents the largest series of patients with angioedema. Although retrospective in nature, the data show that black patients are at a higher risk for ACEI-induced angioedema.     

Perioperative treatment of a patient with hereditary angioedema (HAE) in a case of a young patient with osteosynthesis from a femoral fracture

The following case report describes hereditary angioedema (HAE) in a juvenile male patient presenting with femoral fracture. The clinical characteristics, pathophysiological changes, diagnostics and management of anaesthesia for patients with hereditary angioedema will be discussed. Hereditary angioedema (HAE) is a rare autosomal dominant disorder, which is caused by congenital deficiency of functional C1-inhibitor (C1-INH). Patients are suffering from episodic and painless edema of the skin (face and limbs) and mucous membranes of the respiratory and gastrointestinal tracts (the latter causing abdominal cramps due to edema of the intestine). Life-threatening airway obstruction may occur when patients develop laryngeal edema. It is important to differentiate HAE from the more frequent allergic angioedema because of differences in the pharmacological treatment of acute attacks of HAE. C1-INH-concentrate is effective in both treatment of acute attacks and prevention of edema, especially in children, juveniles and young women.     

Mucopolysaccharidoses: anesthetic considerations and clinical manifestations

Mucopolysaccharidosis (MPS) is a group of genetic disorders that presents challenges during anesthetic care and in particular difficulty with airway management. Patients should be managed by experienced anesthesiologists at centers that are familiar with these types of conditions. Rarely encountered disease states have been identified as important topics in the continuing education of clinical anesthesiologists. This review will define MPS, describe the pathophysiology of MPS, describe how patients with this rare lysosomal storage disorders have dysfunction of tissues, cite the incidence of MPS, list the clinical manifestations and specific problems associated with the administration of anesthesia to patients with MPS, present treatment options for patients with MPS, define appropriate preoperative evaluation and perioperative management of these patients, including, to anticipate potential postoperative airway problems.     

Prise en charge anesthésique d’un accouchement chez une patiente atteinte d’un déficit en inhibiteur de C1 estérase

Hereditary and acquired angioedema (HAE/AAE) are the clinical translation of a qualitative or a quantitative deficit of C1 esterase inhibitor (C1 INH). The frequency and severity of clinical manifestations vary greatly, ranging from a moderate swelling of the extremities to obstruction of upper airway. Anaesthesiologists and intensivists must be prepared to manage acute manifestations of this disease in case of life-threatening laryngeal edema. Surgery, physical trauma and labour are classical triggers of the disease. The anaesthesiologists should be aware of the drugs used as prophylaxis and treatment of acute attacks when considering labour and caesarean section. Androgens are contraindicated during pregnancy. If prophylaxis is required, tranexamic acid may be used with caution. The safest obstetric approach appears to be to administer a predelivery infusion of C1 INH concentrate. It is important to avoid manipulation of the airway as much as possible by relying on regional techniques. We report the case of a patient suffering from an HAE discovered during pregnancy. The management included administration of C1 INH during labor and early epidural analgesia for pain relief. A short review of the pathophysiology and therapeutic options follows.     

Abordagem perioperatória de grávida com angioedema hereditário submetida a cesariana: relato de caso

Hereditary angioedema is an autosomal dominant disorder, presenting as sudden and recurring episodes of variable severity of subcutaneous and mucosa edema that may occur spontaneously or in response to triggers. There are three knwon types of hereditary angioedema. The disorder is caused by decrease in the plasma level or change in the functional capacity of C1 inhibitor, with increase in bradykinin and in vascular permeability, and consequent edema. Several measures are required in the perioperative period in order to avoid an acute attack. Prophylaxis should be carried out throughout pregnancy before any surgical procedure, before dental procedures, upon airway handling, on patients with previous episodes of angioedema, and when there are significant changes in volemia. The literature is scarce in regard to the association between hereditary angioedema and pregnancy. We describe a successful case of a pregnant patient with type I hereditary angioedema submitted to a C‐section.     

Documentation on the anesthetic record: correlation with clinically important variables

PURPOSE: A survey was undertaken at a single Academic Health Sciences Centre to document the opinions of anesthesiologists regarding what variables are important to document on the anesthetic record. A subsequent chart review of anesthetic records was undertaken to determine the extent to which these anesthesiologists record the variables they consider important. METHODS: A survey form was mailed to all practicing staff anesthesiologists at the four adult McGill University affiliated hospitals. Anesthesiologists were asked to rank 23 preoperative and 33 intraoperative variables on a scale from 1-5: (1 = essential; 2 = important; 3 = useful; 4 = not important; 5 = excessive information). All variables considered by consensus < or = 2 (important to essential) were then assessed as to whether they were recorded on 60 charts randomly selected from each of the four teaching hospitals. Only anesthetic records completed by staff anesthesiologists were evaluated. RESULTS: Ninety percent (47/52) of survey forms were completed and returned. Preoperative variables considered most important to document included examination of the patient's airway and allergy status. Intraoperative variables considered most important for documentation were the patient's vital signs. The only variable to have been recorded on all the anesthetic records was the anesthesiologist's name. The allergy status was the most recorded preoperative variable (84% of charts). The recording rates of intraoperative variables ranged from 100% (anesthesiologist's name, start time of anesthesia) to 24% (estimated blood loss). CONCLUSION: McGill anesthesiologists consider many preoperative and intraoperative variables to be important to document on the anesthetic record. However, subsequent chart review indicated that many of these variables are recorded inconsistently. The transmission of anesthesia-related medical information might be improved if anesthesiologists recorded more consistently information they consider to be important.     

Effect of preoperative angiotensin converting enzyme inhibitor or angiotensin receptor blocker use on the frequency of atrial fibrillation after cardiac surgery: a cohort study from the atrial fibrillation suppression trials II and III.

BACKGROUND: Two recent meta-analyses demonstrated that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the risk of developing new-onset atrial fibrillation (AF) by nearly 50%. However, the ability of ACEIs or ARBs to prevent postoperative atrial fibrillation (POAF) after cardiac surgery has not been adequately evaluated. Objective: To evaluate the impact of preoperative ACEI or ARB use on the incidence of POAF after cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting and/or valvular surgery from the (atrial fibrillation suppression trials II and III (AFIST II and III) randomized, controlled trials were evaluated in this cohort evaluation. Data in respect to patient demographics, surgical characteristics, medication utilization and the incidence of POAF (defined as AF lasting at least 5 min in duration documented by telemetry) were all uniformly and prospectively collected as part of AFIST II and III. Multivariate logistic regression was utilized to calculate adjusted odds ratios with 95% confidence intervals. RESULTS: A total of 338 patients were evaluated of which 175 (51.8%) received an ACEI or ARB preoperatively and 163 (48.2%) did not. The study population was 65.7+/-9.1 years of age, 77.8% were male, 11.2% underwent valve surgery, 3.6% had prior AF, 10.1% had heart failure and 84.0 and 37.9% received postoperative beta-blockade and prophylactic amiodarone, respectively. In total, 110 (32.5%) patients developed POAF. Upon multivariate logistic regression, the preoperative use of an ACEI or ARB was not found to be associated with a statistically significant reduction in POAF (adjusted odds ratio; 0.71, 95% CIs 0.42-1.20). CONCLUSIONS: Although preoperative ACEI or ARB use reduced the odds of developing POAF by 29%, this association with not found to be statistically significant. A study with approximately 600 subjects would be needed to discern if ACEIs or ARBs truly impact POAF.     

Airway obstruction due to late-onset angioneurotic edema from angiotensin-converting enzyme inhibition

PURPOSE: Angioneurotic edema is a well-documented complication of angiotensin-converting enzyme inhibitors (ACEI). We report a case of acute airway obstruction from a late-onset, probable ACEI-related angioneurotic edema and its subsequent management. CLINICAL FEATURES: A 48-yr-old obese man presented for transurethral resection of a bladder tumour (TURBT). His past medical history included hypertension controlled with hydrochlorothiazide and quinapril which had been started 13 mo earlier. Previous surgery was uncomplicated. Midazolam was used for premedication and for intraoperative sedation together with fentanyl and propofol. After uneventful spinal anesthesia with bupivacaine, operation and recovery, he was transferred to the floor. Five hours later he developed severe edema of his face, tongue and neck, with drooling, that progressed into airway obstruction and respiratory arrest. Ventilation was restored via immediate cricothyroidotomy, and a subsequent tracheotomy was completed uneventfully in the operating room. His serum C1 esterase inhibitor levels at 1, 5 and 23 days later were normal. The angioneurotic edema was attributed to the ACEI treatment. The edema resolved after 48 hr, and further follow-up was unremarkable. CONCLUSION: This observation is consistent with other reports that angioneurotic edema from ACEI can occur many months after the initiation of treatment. This can involve the airway and may produce life-threatening respiratory compromise. Physicians should be aware of this association and the possible need for immediate surgical intervention for the establishment of an airway in case of worsening edema or respiratory arrest.     

Unanticipated difficult endotracheal intubations in patients with cervical spine instrumentation

We present two cases of unanticipated difficult airway in patients requiring reoperation after cervical spine instrumentation. In both cases, the upper airway examination was normal, and fiberoptic-guided intubation proceeded with the patient sedated and breathing spontaneously. Cord visualization was difficult, but the scope was eventually advanced into the trachea and the endotracheal tube placed safely. Later review of radiographs showed the previously unrecognized protrusion of cervical hardware into the meso- and hypopharynx. We recommend that anesthesiologists review recent radiographic studies for potential airway compromise before approaching the airway of patients presenting for revision of cervical instrumentation.     

Effect of calcium channels blockers and inhibitors of the renin-angiotensin system on renal outcomes and mortality in patients suffering from chronic kidney disease: systematic review and meta-analysis

Background: The renoprotective effect of inhibitors of renin-angiotensin system (RAS) has been identified through placebo-controlled trials. However, the effect of calcium-channel blockers (CCBs) on renal system is still controversial. Our current meta-analysis includes available evidences to compare the effect of dihydropyridine CCBs and ACEIs or ARBs on renal outcomes and mortality. We also further investigate whether CCBs can be used in combination with inhibitors of RAS to improve the prognosis of patients with chronic kidney disease (CKD). Methods and results: Electronic databases were searched up to July 2012, for clinical randomized controlled trials, assessing the effect of dihydropyridine CCBs on the incidence of end-stage renal disease (ESRD) and all-cause mortality in contrast to ACEIs or ARBs. Eight clinical trials were included containing 25,647 participants. ESRD showed significantly higher frequency with CCBs therapy compared with ACEIs or ARBs therapy, though blood pressure was decreased similarly in both groups in every trial (OR, 1.25; 95% CI, 1.05–1.48; p?=?0.01). In contrast, there was no significant difference in the incidence of all-cause mortality between these two groups, though ACEIs or ARBs exhibited better renoprotective effect compared to CCBs (OR, 0.96; 95% CI, 0.89–1.03; p?=?0.24). Conclusions: CCBs did not increase all-cause mortality incidence in patients with CKD though they displayed weaker renoprotective, compared to ACEIs or ARBs therapy. Our results suggest the combination of a CCB and an ACEI or ARB should be a preferable antihypertensive therapy in patients with CKD, considering their higher effect in decreasing blood pressure and fewer adverse metabolic problems caused.     

Case of facial edema and tongue swelling after aortic surgery in the lateral position

The facial edema and tongue swelling after oral surgery are not rare complications and many case reports were published, but they were limited after anesthesia for surgery of other parts. A 70-year-old woman who had underwent thoraco-abdominal aortic graft surgery showed severe facial edema and tongue swelling after the surgery in the right lateral position. The tongue was largely protruded outside of the mouse when entering ICU and was gradually improved. Twelve hours later, the tongue was shrunken into the mouse. The patient was moved to a general ward without any complications on the 5th postoperative day. The patient had taken anti-hypertensive drugs including candesartan for a long period. She might have become susceptible to angioedema by angiotensin receptor blocker such as angiotensin-converting enzyme inhibitor and stress of surgery, and anesthesia might have induced a complication of the acute tongue swelling. Although, prevention and treatment of angioedema have not been established, careful observation would be required.     

Angiotensin-converting enzyme inhibitor-induced isolated visceral angioedema in a liver transplant recipient

Isolated visceral angioedema is an extremely rare complication of angiotensin-converting enzyme inhibitors (ACEIs). We report the first known case of ACEI-associated visceral angioedema occurring in a liver transplant recipient who presented with acute-onset abdominal pain, nausea, vomiting, diarrhea, radiologic findings of small bowel edema, and ascites. Heightened awareness of the phenomenon of isolated ACEI-associated visceral angioedema is necessary given the increasing use of these medications for treating hypertension related to calcineurin inhibitors and the need to avoid unnecessary surgical or diagnostic interventions in solid-organ transplant recipients.     

The effects of ACE inhibitor treatment and ACE gene polymorphism on erythropoiesis in chronic hemodialysis patients

Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.