*(:hief, Anesthesia Section, Warren (;. Magnuson Clinical Center; Associate Professor ot Anesthesia, Georgetown University Medical Center ?Lieutenant, Medical Corps, U.S. Naval Reserve; Staff‘ Anesthesiologist, Department ol Anesthesia, National Naval Medical Center, Bethesda, MD $Anesthesia Section, Warren (;. Magrruson Clinical Center; Instructor of’ Anesthesia, (Geol-getown University Medical (Ienter IHead, Bacterial Diseases Section, Institute of‘Allergy and Infectious National Institutes of Health
National Diseases,
/Special Assistant to Director of Division of Intramural Research, Bacterial Diseases Section, National Institute of Allergy and Intkctious Diseases, National Institutes of Health #Head, Thoracir Oncology Section, National Cancer Institute. National Institutes of Health
Anesthetic Considerations in Patients with Chronic Granulomatous Disease Russell T. Wall, MD,* Charles A. Buzzanell, MD,? Todd A. Epstein, MD& Harry L. Malech, MD&j David Melnick, MD,11 Harvey I. Pass, MD,# John I. Gallin, MD** Departments G. Magnuson
(,‘hronic
of Anesthesia, Bacterial Diseases, and Thoracic Oncology, Warren Clinical Center, National Institutes of Health, Bethesda, MD.
grudomatou~
churclcterizd orgunism~ cd Long-term
Address reprint requests to Dr. Wall at the Anesthesia Section, Warren G. Magnuson Clinical Center (XX24), National Institutes of Health, Bethesda, MD 20892, USA. The content and opinions of‘ this article reIlect the personal opinions of‘the co-authors and in no way state policy from the Navy Medical Department or Department of’ Defense.
Received for publication january revised manuscript April 2, IWO.
accepted
0 1990 Butterworth-Heinemann
306
.J. Clin. Anesth.,
IO, 1990; f’or publication
(CGD)
U u ruw, g~~rwtirally truns mittd
life-threatenirlt:
fwesLsiw i~flummutory
prophylactic.
antimicrobial
infections
ret&ions qpts
disorder
with c.cLtnlusP-po,~iti-i,Pmicro-
that led
to ~punuloma
nnd uggressiw
formutiow
.surgirul m&qment
ure thr mainstu~s of th~rupy. Thu uuthors prouideed unr.rthetics for 17 putiu,~t.s with CGD under&g
**Director, Division of Intramural Research Program, Bacterial Diseases Section, National Institute of’Allergy and Infectious Diseases. National Institutes of Health
diseuw
by recurrent,
multiple
orpu
j5 ,suqical
i,l the ~urioperut~ue period. muy predispow Keywords:
chromosome anesthesia.
procdures.
svstrm in-idvrm~vzt
Granulomutous
,such putients Granulomatous
abnormalities;
These putirnts pres&rd
und were ut .significunt lesions
to .surg~~ with
risk for com~licutions
ofthe gustrointe.stinnl
(GI) truc’t
to regurgitution~ and asj%rution.
disease, chronic; lung phagocytosis; NADP;
diseases, catalase;
t‘ungal; aspergillus;
Introduction Chronic granulomatous disease (CGD) is a rare, genetically transmitted disorder characterized by recurrent, lif’e-threatening inftctions with catalase-positive microorganisms and excessive inflammatory reactions that lead to granuloma formation. Its incidence is about 1 in 1 ,OOO,OOOpersons. Most cases of’the disease are transmitted in an X-linked recessive fashion (650/c), but some patients have an autosomal recessive pattern of’ inheritance (34%) and some have an autosomal dominant pattern with variable
vol. 2, September/October
1990
penetration. It represents a disorder of phagocyte (neutrophil and monocyte) function characterized by deficient nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation.’ Phagocytes of patients with CGD do not respond to particulate or soluble stimuli with a normal “respiratory burst”-an increase in oxygen uptake resulting in a coordinated series of metabolic events that produce several highly reactive microbicidal agents [j.~., superoxide (OF) and hydrogen peroxide (H,O,)] by partial oxygen reduction. It is believed that catalase-positive microorganisms destroy any residual H,O, produced by defective phagocytes or by the oxidative respiration of the microorganisms. As a result, the phagocytes of patients with CGD and defective H,O, generation are without a complete antimicrobial systenl.‘-x CGD often presents in infancy or early childhood. frequency and seIt is manifested by an increased verity of deep-tissue infections with catalase-positive bacteria and fungi and recurrent severe infections that heal slowly and resist treatment. Sites of infection, in descending order of frequency, are lung (greatel than 50%), lymph nodes, skin, soft tissue, liver, GI blood, genitourinary tract, eye, and tract, bone, t~rain.Z~‘.x In more than 55% of the episodes, no organism is recovered. Stuphy~ococcus UUTUO is the most common organism causing febrile episodes followed ~tiol(twt~ ttt, I-‘.seutLoby [email protected] ,sp., Ckromohnctr~iurrt rnouus wpacia, and Nocartlin.’ Before the use of long-term prophylactic antimicrobial agents and aggressive surgical management, the clinical course was one of repeated and protracted infections, with death from infection occurring in the first or second decade of life. Chronic antibiotic prophylaxis has slowed the disease course. Survival seems to be prolonged, and hospitalizations are less frequent, but serious complications of imperfectly suppressed infections often develop. These complications include strictures of the GI and genitourinary tracts and chronic lung disease with fibrosis and bronchectasis. Death often results from fungal infections, particularly Aspuyqil1u.s ,sp. CGD infection may present with only a low-grade fever. Increases in leukocyte counts are rare. An increased erythrocyte sedimentation rate is a particularly reliable blood test to suggest an infection.” Management of CXD includes long-term antibiotic prophylaxis (trimethoprim-sulfamethoxazole) and vigorous treatment of acute infections with parenteral antibiotics (a penicillinase-resistant penicillin and an aminoglycoside), as well as surgery, if indicated. Once parenteral antimicrobial therapy is begun for major infection, it should be continued for 2 to 4 weeks.?
Localized sites of infection require aggressive surgical intervention for diagnostic and therapeutic reasons. ‘I‘horough debridement and prolonged drainage are necessary. White blood cell transfusions also have been used effectively.‘.” ‘I‘ransfused white blood cells appear to arrive at inflammatory foci functionally intact. H&1, likely diffuses from the normal cells into the CGD cells. It is suspected that a few normal cells may have the ability to “normalize” multiple CGD cells. Leukocyte transfusions in the immediate (less than :1 days) postoperative period must be used with caution, since the delivery of normal neutrophils to the lung could theoretically mediate free radical-type injury. Cure of some congenital phagocyte defects by bone marrow transplantation have been reported.‘” Howe\ er, c.oml’licatioIls with bone marrow transplantation are prevalent, and this form of’ therapy is not used for most patients. Since the genes for all four known hereditary forms of CGD have been cloned, gene therapy may be a promising long-term treatment modality for this phagocyte defect. Recombinant human iliterferon-y reconstitutes phagoc?tic bactericidal acti\.it): with an associated increase m superoxide productlon in (X;D patients.”
A S-year-old, 13 kg boy with ASA physical status II and CGD was scheduled for elective placement of a Hickman catheter. ‘I-he patient was diagnosed with (: undergoing 55 surgical procedures. The patients were 13 males and 4 females ranging in age from 3 to 30 years. Twelve patients had the CGD diagnosis confirmed before 2% years of age, and the remaining patients were diagnosed at 5, 14, 14, 17, and 25 years of age. All patients had at least two 308
.J. Clin. Anesth.,
vol. 2, September/October
1990
Table 1.
1’~
Medical
Historks Number
Pathology
of Patients Pathology*
with
Pulmoria~-y (pieurrionia, lung abscess, dilluse
in
I3 II
filtrates, empyerna) Dermatitis Hepatic abscess(es) Lymphactenitis Soft-tissue infections Entrrocolitis Osteomyelitis BI-ilit
!I !) H
4
AhSC’C5S
Sepsis Intro-abclor~~ir~a1 abscess Otitis, pericarditis, pelvic :~l)scess. sinusitis * I‘otal rr~tnbcr of patients
2 ‘)
= 17
infections requiring hospitalization before their first surgical procedure at the Clinical Center. Past medical problems were frequent, with many infections requiring surgery (Table 1). The ASA physical status classification of patients for the 55 surgical procedures included 30 patients with ASA status II, 23 patients with ASA status III, and 2 patients with ASA status IV. Four procedures were performed on an emergency basis. Securing central venous access via Hickman catheter placement (15 cases) and debridement of surgical wounds (12 cases) were the leading indications for surgery (Table 2).
Monitoring devices for each case included an automated BP cuff, EKG, precordial and/or esophageal stethoscope, temperature probe, pulse oximeter, endtidal CO, monitor, and 0, analyzer in the inspiratory limb of the breathing circuit. Radial artery catheters for direct BP monitoring were inserted in all patients undergoing intrathoracic and intra-abdominal surCentral venous pressure (CVP) gical procedures. monitoring was not initiated in any cases. On several occasions, however, patients came to the operating room (OR) with Hickman catheters in place, and these devices were used for monitoring CVP. In 5 1 cases, general endotracheal anesthesia was administered; in 1 case, general anesthesia was delivered with a face mask; and in 3 cases, monitored anesthesia care was provided. All patients having intrathoracic and intra-abdominal procedures were transported to the ICXJ following surgery. Patients having other procedures were transported to the recovery room.
Table 2.
Procedures
and Indications
Procedure
Number of Cases
Indication
Hickman catheter placement Debridement of surgical wounds Thoracotomy and segmentectomy (2); lobectomy (4); open lung biopsy (2); drainage of empyema (1) Excise soft-tissue mass I 8c D soft-tissue abscess I & D liver abscess(es) Closure of sufgical wound Gystoscopy with stent placement Cholecystectorriy Dental restorations
15 12 !I
Administer intravenous antibiotic and/or antifungal therapy ‘1‘reat infection Remove fimgal or bacterial abscess, diagnose etiology of’in-
Results In addition to the complication outlined in the case report, several complications occurred in the intraoperative and immediate (less than 48 hours) postoperative periods (Tub& 3). One patient regurgitated during an inhalation induction of general anesthesia, requiring immediate intubation and postponement of surgery. No aspiration of gastric contents occurred, and the patient recovered satisfactorily. One patient experienced laryngospasm upon extubation in the OR and required immediate reintubation. The laryngospasm was precipitated by excessive airway secretions, and the patient was safely extubated shortly thereafter. A third patient developed pseudomonas sepsis following a thoracotomy and lobectomy for removal of a lung abscess and required extended treatment in the ICU. A fourth patient developed pneumonia and experienced respiratory distress at 48 hours postoperatively, requiring treatment in the ICU. She died from respiratory insufficiency on the third day after surgery. Also, several postoperative complications occurred after 48 hours (Table _?). Intrathoracic surgery presented unique challenges. Pulmonary function tests on three patients before surgery showed that two had mild to moderate lung disease, and the patient who died 3 days after surgery had severe restrictive and obstructive disease. Past and present pulmonary pathology (i.e., fibrosis) made surgery exposure extremely difficult in all intrathoracic cases. One-lung ventilation was very useful in providing optimal surgical conditions. Seven patients received one-lung ventilation, three via a double-lumen endobronchial tube and four by a single-lumen endotracheal tube placed in the main-stem bronchus of the ventilated lung by fiber-optic bronchoscopy. The
filtrate,
or drain
empyema
For diagnosis ‘Treat infection Treat infection Close wound Obstruction of genitourinary Chronic cliolec-ystitis Multiple caries
tract
latter four patients were too small for a double-lumen endobronchial tube to fit comfortably through the larynx. Isolation of one lung from the other to avoid spillage or contamination was not the indication for one-lung ventilation in those cases involving a lung abscess, since these abscesses were documented to be well loculated. However, such an absolute indication for one-lung anesthesia (i.e., bronchiectasis and/or draining abscesses) may be present in this patient population. One patient who needed multiple surgical procedures required meticulous positioning. This patient had an unstable spine secondary to osteomyelitis of multiple (‘I&-12) vertebral bodies and ribs. A bed board was necessary to ensure immobilization in transporting and lifting this patient.
Discussion Patients with CGD present a challenge to the anesthesiologist. The majority of patients present with an infectious process requiring surgical drainage. Preoperatively, the total medical condition of the patient must be appreciated. Although the patient may present with a localized infection that is easily accessible to surgical intervention, other organ systems may demonstrate the sequelae of CGD. The lung is the most frequent site of infection. Pulmonary pathology may range from a localized abscess to a diffuse granulomatous involvement or extensive fibrosis. Preoperative pulmonary function tests may be indicated in cases of extensive involvement. Arterial blood gases should be performed in patients requiring anatomic resection (lobectomy or pneumonectomy). In patients J. Clin. Anesth.,
vol. 2, September/October
1990
309
Table 3.
l)dta on I’erioperdtive
(:o~npli~~~iiorl~
Age (yr)
Race/Sex
Operation
3
WIM
4
W/M
4
W/M
Hickman catheter placement Wound ciebridement ‘I‘horacotomy, lot~eclonly
27
B/F
2!)
W/M
7
W/M
Complication
Time of Complication
Kegurgitation
Treatment
Outcome
Intubation
NO ilsl~il~;lliOtr F:xtiib;itc~tl with out lMd,lcrll Kesolution of’ sellsis
I.al~yngosl~asnl
Jrltraol~er;lti\el\
Keintubation
Sepsis
4x 11 l~ostol~er~rtivel~~
Atelectasis 2” IO bronchial I~LKLIS
>48 11 l,ostoperativel~~
aLlpport
20
n/E‘
20
n/F
3
B/M
18
W/M
Thoracotonly;, lobectomy ‘l‘horacotomy, open lung biopsy Incision and drainage of soFt-tissue abscesses Thoracotomy, lobectomy Hickman catheter placement ‘I‘horacotomy, lobectomy Incision arid drainage of liver abscess
rlLl$ Heptltis 2” 5fluoroc~tosine Kespiratory’ distress 2” to respiratory infection Hractiial plexus palsy
who have had previous pulmonary resection for CGD, with marginal (FEV, less than 1.5 liters) pulmonary reserve, computerized quantitative ventilation perfusion scanning has been performed. ‘This procedure has been particularly useful in patients with large central lesions in whom a segmental or lobar resection is anticipated to ensure that the postoperative residual lung function is adequate. Hepatic pathology may be significant. More than half the authors’ patients had prior surgery for treatment of hepatic abscesses. Surgery ranged from incision and drainage of an abscess to the removal of an entire lobe of the liver. Such extensive pathology may have an important effect on liver function. Obstructive granulomatous lesions of the GI tract may lead to delayed gastric emptying or dysfunction of the gastroesophageal sphincter. Such pathology is not infrequent. ‘I’ As a result, the authors recommend a rapid-sequence induction to administer general anesthesia to all patients with CO. Other sites of involvement, including skin and soft tissue, genitou310
,J. Clin. Anesth.,
vol. 2, September/October
1990
>4x h l)ostol~er;rti\~el~
>48 h l~ostoperativrl~ >48 h l)ostol~er;itivrl~~ Intraopel-;ttivel~ OI postoperatively
I(:U,
I)/(: aniphotrric~in
I:.xpiretl 2” to respil-ator-\, irrsuf’t’ic~ierq Kesolutiott of I-enal iiisulfi&nq Kesotlrtion of’ rc~l;ll irisul’l i( irrrc-! Kesolution 01 atetcc tasis
I)/(: .‘,-ll~~o~~oc~ytosilre Kesolutiorr 01’ hrpiltili5 I(:IT, alltibiotics, Kesolution 01 hemotlynamic ir1t.c tion supl~ol~t Physical therap! Kesolutiotl of IMlS,
rinary tract, bone, and blood, may present preoperative considerations. III addition to the disease process itself, the recommended therapies may have an adverse effect on organ function. The extensive use of aminoglycosides and amphotericin K can alter renal function. The use of these agents should be closely monitored. Many patients with CGD who require surgery are children. Most have had multiple and prolonged hospitalizations and have undergone numerous surgical procedures in the past, and they are frequently anxious and frustrated. Also, some of these patients are receiving narcotic infusions for pain control. As a result, premeditation requirements may vary considerably and must be individualized. Many CGD patients receive leukocyte transfusions sometime during their hospitalization. Glucocorticoid therapy may be used preoperatively to suppress febrile responses to leukocyte transfusions. If it is, steroid supplementation in the perioperative period may be indicated.
‘I-he availability of blood for surgery may be affected, since a minority of patients with the X-linked form of CCD have abnormalities in the Kell blood group system (McCloud syndrome), which may cause difficulties with compatibility testing. The M&loud syndrome’s genetic locus lies adjacent to the X-linked CGD gene on the X chromosome, and occasional X-linked CGD kindreds have a large deletion encompassing both of these gene loci. Intraoperatively, anesthetic management is influenced by the degree of various organ system dysfunction created by the disease. The use of extensive hemodynamic monitoring depends on the patient’s medical condition and the surgery performed. For intrathoracic procedures requiring significant lung dissection, the use of one-lung anesthesia, if tolerated by the patient, may be very helpful in facilitating surgical exposure and dissection and may be essential in cases involving possible spillage of infectious material from the operated lung to the nonoperated one. Postoperatively, possible infection of various sites (intravascular catheters, urinary tract, wound, or pulmonary system) must be aggressively monitored and treated. The mainstay of postoperative treatment is prolonged drainage of the surgical area, prolonged parenteral antibiotic, and, possibly, antifungal therapy. Pain control requiring parenteral narcotics is usually necessary for the first 24 to 48 hours postoperatively. Dressing changes may require parenteral analgesics, and debridements usually require general anesthesia.
2. Gallin JI, Buescher E, Seligmann BE, Nath J, Gaither T, Katz P: Recent advances in chronic granulomatous disease. Ann Intern Med 1983;99:657-74. :1. Mills EL, Quie PC;: Inheritance of. chronic granulomatous disease. In: Gallin JI, Fauci AS, eds. Advanc~.c itr Host Drfkse Disww.
Cw
RCU Clitt Lab Sri
197733:X I- 103.
5. Regelmann
W, Hays N, Quie PG: Chronic granulomatous disease: historical perspectives and the clinical experience at the Universitv of’ Minnesota Hospitals. In: (Xin ,JI. Fauci AS, eds. A<r?cc.r,\ itr Has/ Deferw
~~l~~ttrttti,~ttt.c. Vol.
3: (,lrottic
(;rcltrttlottto/ott\
Discwe.
New
\.ork: Ra\,en Press 19X3;%24. H. DonowitL GR, Mandell (;L.: (Xnical presentation and unusual inf’ections in chronic ~r:l.alilllorrlatous disease. In: (;allin ,JI, Fauci AS, eds. Ad7~ff11cf~.~ m Ha.sl D$erw 121p~lttttli.\ttt).\. Vol.
9.
10.
1 I.
12. BM: The nature of‘ the NADPH oxidase. In: Gallin JI, Fauci AS, eds. Advances in Host D
National Diseases,
/Special Assistant to Director of Division of Intramural Research, Bacterial Diseases Section, National Institute of Allergy and Intkctious Diseases, National Institutes of Health #Head, Thoracir Oncology Section, National Cancer Institute. National Institutes of Health
Anesthetic Considerations in Patients with Chronic Granulomatous Disease Russell T. Wall, MD,* Charles A. Buzzanell, MD,? Todd A. Epstein, MD& Harry L. Malech, MD&j David Melnick, MD,11 Harvey I. Pass, MD,# John I. Gallin, MD** Departments G. Magnuson
(,‘hronic
of Anesthesia, Bacterial Diseases, and Thoracic Oncology, Warren Clinical Center, National Institutes of Health, Bethesda, MD.
grudomatou~
churclcterizd orgunism~ cd Long-term
Address reprint requests to Dr. Wall at the Anesthesia Section, Warren G. Magnuson Clinical Center (XX24), National Institutes of Health, Bethesda, MD 20892, USA. The content and opinions of‘ this article reIlect the personal opinions of‘the co-authors and in no way state policy from the Navy Medical Department or Department of’ Defense.
Received for publication january revised manuscript April 2, IWO.
accepted
0 1990 Butterworth-Heinemann
306
.J. Clin. Anesth.,
IO, 1990; f’or publication
(CGD)
U u ruw, g~~rwtirally truns mittd
life-threatenirlt:
fwesLsiw i~flummutory
prophylactic.
antimicrobial
infections
ret&ions qpts
disorder
with c.cLtnlusP-po,~iti-i,Pmicro-
that led
to ~punuloma
nnd uggressiw
formutiow
.surgirul m&qment
ure thr mainstu~s of th~rupy. Thu uuthors prouideed unr.rthetics for 17 putiu,~t.s with CGD under&g
**Director, Division of Intramural Research Program, Bacterial Diseases Section, National Institute of’Allergy and Infectious Diseases. National Institutes of Health
diseuw
by recurrent,
multiple
orpu
j5 ,suqical
i,l the ~urioperut~ue period. muy predispow Keywords:
chromosome anesthesia.
procdures.
svstrm in-idvrm~vzt
Granulomutous
,such putients Granulomatous
abnormalities;
These putirnts pres&rd
und were ut .significunt lesions
to .surg~~ with
risk for com~licutions
ofthe gustrointe.stinnl
(GI) truc’t
to regurgitution~ and asj%rution.
disease, chronic; lung phagocytosis; NADP;
diseases, catalase;
t‘ungal; aspergillus;
Introduction Chronic granulomatous disease (CGD) is a rare, genetically transmitted disorder characterized by recurrent, lif’e-threatening inftctions with catalase-positive microorganisms and excessive inflammatory reactions that lead to granuloma formation. Its incidence is about 1 in 1 ,OOO,OOOpersons. Most cases of’the disease are transmitted in an X-linked recessive fashion (650/c), but some patients have an autosomal recessive pattern of’ inheritance (34%) and some have an autosomal dominant pattern with variable
vol. 2, September/October
1990
penetration. It represents a disorder of phagocyte (neutrophil and monocyte) function characterized by deficient nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation.’ Phagocytes of patients with CGD do not respond to particulate or soluble stimuli with a normal “respiratory burst”-an increase in oxygen uptake resulting in a coordinated series of metabolic events that produce several highly reactive microbicidal agents [j.~., superoxide (OF) and hydrogen peroxide (H,O,)] by partial oxygen reduction. It is believed that catalase-positive microorganisms destroy any residual H,O, produced by defective phagocytes or by the oxidative respiration of the microorganisms. As a result, the phagocytes of patients with CGD and defective H,O, generation are without a complete antimicrobial systenl.‘-x CGD often presents in infancy or early childhood. frequency and seIt is manifested by an increased verity of deep-tissue infections with catalase-positive bacteria and fungi and recurrent severe infections that heal slowly and resist treatment. Sites of infection, in descending order of frequency, are lung (greatel than 50%), lymph nodes, skin, soft tissue, liver, GI blood, genitourinary tract, eye, and tract, bone, t~rain.Z~‘.x In more than 55% of the episodes, no organism is recovered. Stuphy~ococcus UUTUO is the most common organism causing febrile episodes followed ~tiol(twt~ ttt, I-‘.seutLoby [email protected] ,sp., Ckromohnctr~iurrt rnouus wpacia, and Nocartlin.’ Before the use of long-term prophylactic antimicrobial agents and aggressive surgical management, the clinical course was one of repeated and protracted infections, with death from infection occurring in the first or second decade of life. Chronic antibiotic prophylaxis has slowed the disease course. Survival seems to be prolonged, and hospitalizations are less frequent, but serious complications of imperfectly suppressed infections often develop. These complications include strictures of the GI and genitourinary tracts and chronic lung disease with fibrosis and bronchectasis. Death often results from fungal infections, particularly Aspuyqil1u.s ,sp. CGD infection may present with only a low-grade fever. Increases in leukocyte counts are rare. An increased erythrocyte sedimentation rate is a particularly reliable blood test to suggest an infection.” Management of CXD includes long-term antibiotic prophylaxis (trimethoprim-sulfamethoxazole) and vigorous treatment of acute infections with parenteral antibiotics (a penicillinase-resistant penicillin and an aminoglycoside), as well as surgery, if indicated. Once parenteral antimicrobial therapy is begun for major infection, it should be continued for 2 to 4 weeks.?
Localized sites of infection require aggressive surgical intervention for diagnostic and therapeutic reasons. ‘I‘horough debridement and prolonged drainage are necessary. White blood cell transfusions also have been used effectively.‘.” ‘I‘ransfused white blood cells appear to arrive at inflammatory foci functionally intact. H&1, likely diffuses from the normal cells into the CGD cells. It is suspected that a few normal cells may have the ability to “normalize” multiple CGD cells. Leukocyte transfusions in the immediate (less than :1 days) postoperative period must be used with caution, since the delivery of normal neutrophils to the lung could theoretically mediate free radical-type injury. Cure of some congenital phagocyte defects by bone marrow transplantation have been reported.‘” Howe\ er, c.oml’licatioIls with bone marrow transplantation are prevalent, and this form of’ therapy is not used for most patients. Since the genes for all four known hereditary forms of CGD have been cloned, gene therapy may be a promising long-term treatment modality for this phagocyte defect. Recombinant human iliterferon-y reconstitutes phagoc?tic bactericidal acti\.it): with an associated increase m superoxide productlon in (X;D patients.”
A S-year-old, 13 kg boy with ASA physical status II and CGD was scheduled for elective placement of a Hickman catheter. ‘I-he patient was diagnosed with (: undergoing 55 surgical procedures. The patients were 13 males and 4 females ranging in age from 3 to 30 years. Twelve patients had the CGD diagnosis confirmed before 2% years of age, and the remaining patients were diagnosed at 5, 14, 14, 17, and 25 years of age. All patients had at least two 308
.J. Clin. Anesth.,
vol. 2, September/October
1990
Table 1.
1’~
Medical
Historks Number
Pathology
of Patients Pathology*
with
Pulmoria~-y (pieurrionia, lung abscess, dilluse
in
I3 II
filtrates, empyerna) Dermatitis Hepatic abscess(es) Lymphactenitis Soft-tissue infections Entrrocolitis Osteomyelitis BI-ilit
!I !) H
4
AhSC’C5S
Sepsis Intro-abclor~~ir~a1 abscess Otitis, pericarditis, pelvic :~l)scess. sinusitis * I‘otal rr~tnbcr of patients
2 ‘)
= 17
infections requiring hospitalization before their first surgical procedure at the Clinical Center. Past medical problems were frequent, with many infections requiring surgery (Table 1). The ASA physical status classification of patients for the 55 surgical procedures included 30 patients with ASA status II, 23 patients with ASA status III, and 2 patients with ASA status IV. Four procedures were performed on an emergency basis. Securing central venous access via Hickman catheter placement (15 cases) and debridement of surgical wounds (12 cases) were the leading indications for surgery (Table 2).
Monitoring devices for each case included an automated BP cuff, EKG, precordial and/or esophageal stethoscope, temperature probe, pulse oximeter, endtidal CO, monitor, and 0, analyzer in the inspiratory limb of the breathing circuit. Radial artery catheters for direct BP monitoring were inserted in all patients undergoing intrathoracic and intra-abdominal surCentral venous pressure (CVP) gical procedures. monitoring was not initiated in any cases. On several occasions, however, patients came to the operating room (OR) with Hickman catheters in place, and these devices were used for monitoring CVP. In 5 1 cases, general endotracheal anesthesia was administered; in 1 case, general anesthesia was delivered with a face mask; and in 3 cases, monitored anesthesia care was provided. All patients having intrathoracic and intra-abdominal procedures were transported to the ICXJ following surgery. Patients having other procedures were transported to the recovery room.
Table 2.
Procedures
and Indications
Procedure
Number of Cases
Indication
Hickman catheter placement Debridement of surgical wounds Thoracotomy and segmentectomy (2); lobectomy (4); open lung biopsy (2); drainage of empyema (1) Excise soft-tissue mass I 8c D soft-tissue abscess I & D liver abscess(es) Closure of sufgical wound Gystoscopy with stent placement Cholecystectorriy Dental restorations
15 12 !I
Administer intravenous antibiotic and/or antifungal therapy ‘1‘reat infection Remove fimgal or bacterial abscess, diagnose etiology of’in-
Results In addition to the complication outlined in the case report, several complications occurred in the intraoperative and immediate (less than 48 hours) postoperative periods (Tub& 3). One patient regurgitated during an inhalation induction of general anesthesia, requiring immediate intubation and postponement of surgery. No aspiration of gastric contents occurred, and the patient recovered satisfactorily. One patient experienced laryngospasm upon extubation in the OR and required immediate reintubation. The laryngospasm was precipitated by excessive airway secretions, and the patient was safely extubated shortly thereafter. A third patient developed pseudomonas sepsis following a thoracotomy and lobectomy for removal of a lung abscess and required extended treatment in the ICU. A fourth patient developed pneumonia and experienced respiratory distress at 48 hours postoperatively, requiring treatment in the ICU. She died from respiratory insufficiency on the third day after surgery. Also, several postoperative complications occurred after 48 hours (Table _?). Intrathoracic surgery presented unique challenges. Pulmonary function tests on three patients before surgery showed that two had mild to moderate lung disease, and the patient who died 3 days after surgery had severe restrictive and obstructive disease. Past and present pulmonary pathology (i.e., fibrosis) made surgery exposure extremely difficult in all intrathoracic cases. One-lung ventilation was very useful in providing optimal surgical conditions. Seven patients received one-lung ventilation, three via a double-lumen endobronchial tube and four by a single-lumen endotracheal tube placed in the main-stem bronchus of the ventilated lung by fiber-optic bronchoscopy. The
filtrate,
or drain
empyema
For diagnosis ‘Treat infection Treat infection Close wound Obstruction of genitourinary Chronic cliolec-ystitis Multiple caries
tract
latter four patients were too small for a double-lumen endobronchial tube to fit comfortably through the larynx. Isolation of one lung from the other to avoid spillage or contamination was not the indication for one-lung ventilation in those cases involving a lung abscess, since these abscesses were documented to be well loculated. However, such an absolute indication for one-lung anesthesia (i.e., bronchiectasis and/or draining abscesses) may be present in this patient population. One patient who needed multiple surgical procedures required meticulous positioning. This patient had an unstable spine secondary to osteomyelitis of multiple (‘I&-12) vertebral bodies and ribs. A bed board was necessary to ensure immobilization in transporting and lifting this patient.
Discussion Patients with CGD present a challenge to the anesthesiologist. The majority of patients present with an infectious process requiring surgical drainage. Preoperatively, the total medical condition of the patient must be appreciated. Although the patient may present with a localized infection that is easily accessible to surgical intervention, other organ systems may demonstrate the sequelae of CGD. The lung is the most frequent site of infection. Pulmonary pathology may range from a localized abscess to a diffuse granulomatous involvement or extensive fibrosis. Preoperative pulmonary function tests may be indicated in cases of extensive involvement. Arterial blood gases should be performed in patients requiring anatomic resection (lobectomy or pneumonectomy). In patients J. Clin. Anesth.,
vol. 2, September/October
1990
309
Table 3.
l)dta on I’erioperdtive
(:o~npli~~~iiorl~
Age (yr)
Race/Sex
Operation
3
WIM
4
W/M
4
W/M
Hickman catheter placement Wound ciebridement ‘I‘horacotomy, lot~eclonly
27
B/F
2!)
W/M
7
W/M
Complication
Time of Complication
Kegurgitation
Treatment
Outcome
Intubation
NO ilsl~il~;lliOtr F:xtiib;itc~tl with out lMd,lcrll Kesolution of’ sellsis
I.al~yngosl~asnl
Jrltraol~er;lti\el\
Keintubation
Sepsis
4x 11 l~ostol~er~rtivel~~
Atelectasis 2” IO bronchial I~LKLIS
>48 11 l,ostoperativel~~
aLlpport
20
n/E‘
20
n/F
3
B/M
18
W/M
Thoracotonly;, lobectomy ‘l‘horacotomy, open lung biopsy Incision and drainage of soFt-tissue abscesses Thoracotomy, lobectomy Hickman catheter placement ‘I‘horacotomy, lobectomy Incision arid drainage of liver abscess
rlLl$ Heptltis 2” 5fluoroc~tosine Kespiratory’ distress 2” to respiratory infection Hractiial plexus palsy
who have had previous pulmonary resection for CGD, with marginal (FEV, less than 1.5 liters) pulmonary reserve, computerized quantitative ventilation perfusion scanning has been performed. ‘This procedure has been particularly useful in patients with large central lesions in whom a segmental or lobar resection is anticipated to ensure that the postoperative residual lung function is adequate. Hepatic pathology may be significant. More than half the authors’ patients had prior surgery for treatment of hepatic abscesses. Surgery ranged from incision and drainage of an abscess to the removal of an entire lobe of the liver. Such extensive pathology may have an important effect on liver function. Obstructive granulomatous lesions of the GI tract may lead to delayed gastric emptying or dysfunction of the gastroesophageal sphincter. Such pathology is not infrequent. ‘I’ As a result, the authors recommend a rapid-sequence induction to administer general anesthesia to all patients with CO. Other sites of involvement, including skin and soft tissue, genitou310
,J. Clin. Anesth.,
vol. 2, September/October
1990
>4x h l)ostol~er;rti\~el~
>48 h l~ostoperativrl~ >48 h l)ostol~er;itivrl~~ Intraopel-;ttivel~ OI postoperatively
I(:U,
I)/(: aniphotrric~in
I:.xpiretl 2” to respil-ator-\, irrsuf’t’ic~ierq Kesolutiott of I-enal iiisulfi&nq Kesotlrtion of’ rc~l;ll irisul’l i( irrrc-! Kesolution 01 atetcc tasis
I)/(: .‘,-ll~~o~~oc~ytosilre Kesolutiorr 01’ hrpiltili5 I(:IT, alltibiotics, Kesolution 01 hemotlynamic ir1t.c tion supl~ol~t Physical therap! Kesolutiotl of IMlS,
rinary tract, bone, and blood, may present preoperative considerations. III addition to the disease process itself, the recommended therapies may have an adverse effect on organ function. The extensive use of aminoglycosides and amphotericin K can alter renal function. The use of these agents should be closely monitored. Many patients with CGD who require surgery are children. Most have had multiple and prolonged hospitalizations and have undergone numerous surgical procedures in the past, and they are frequently anxious and frustrated. Also, some of these patients are receiving narcotic infusions for pain control. As a result, premeditation requirements may vary considerably and must be individualized. Many CGD patients receive leukocyte transfusions sometime during their hospitalization. Glucocorticoid therapy may be used preoperatively to suppress febrile responses to leukocyte transfusions. If it is, steroid supplementation in the perioperative period may be indicated.
‘I-he availability of blood for surgery may be affected, since a minority of patients with the X-linked form of CCD have abnormalities in the Kell blood group system (McCloud syndrome), which may cause difficulties with compatibility testing. The M&loud syndrome’s genetic locus lies adjacent to the X-linked CGD gene on the X chromosome, and occasional X-linked CGD kindreds have a large deletion encompassing both of these gene loci. Intraoperatively, anesthetic management is influenced by the degree of various organ system dysfunction created by the disease. The use of extensive hemodynamic monitoring depends on the patient’s medical condition and the surgery performed. For intrathoracic procedures requiring significant lung dissection, the use of one-lung anesthesia, if tolerated by the patient, may be very helpful in facilitating surgical exposure and dissection and may be essential in cases involving possible spillage of infectious material from the operated lung to the nonoperated one. Postoperatively, possible infection of various sites (intravascular catheters, urinary tract, wound, or pulmonary system) must be aggressively monitored and treated. The mainstay of postoperative treatment is prolonged drainage of the surgical area, prolonged parenteral antibiotic, and, possibly, antifungal therapy. Pain control requiring parenteral narcotics is usually necessary for the first 24 to 48 hours postoperatively. Dressing changes may require parenteral analgesics, and debridements usually require general anesthesia.
2. Gallin JI, Buescher E, Seligmann BE, Nath J, Gaither T, Katz P: Recent advances in chronic granulomatous disease. Ann Intern Med 1983;99:657-74. :1. Mills EL, Quie PC;: Inheritance of. chronic granulomatous disease. In: Gallin JI, Fauci AS, eds. Advanc~.c itr Host Drfkse Disww.
Cw
RCU Clitt Lab Sri
197733:X I- 103.
5. Regelmann
W, Hays N, Quie PG: Chronic granulomatous disease: historical perspectives and the clinical experience at the Universitv of’ Minnesota Hospitals. In: (Xin ,JI. Fauci AS, eds. A<r?cc.r,\ itr Has/ Deferw
~~l~~ttrttti,~ttt.c. Vol.
3: (,lrottic
(;rcltrttlottto/ott\
Discwe.
New
\.ork: Ra\,en Press 19X3;%24. H. DonowitL GR, Mandell (;L.: (Xnical presentation and unusual inf’ections in chronic ~r:l.alilllorrlatous disease. In: (;allin ,JI, Fauci AS, eds. Ad7~ff11cf~.~ m Ha.sl D$erw 121p~lttttli.\ttt).\. Vol.
9.
10.
1 I.
12. BM: The nature of‘ the NADPH oxidase. In: Gallin JI, Fauci AS, eds. Advances in Host D
