Severe group a streptococcal infection and streptococcal toxic shock syndrome

12 Pages·2001·0.24 MB·English

1129
Review Article
Severe Group A
Streptococcal Infection
and Streptococcal Toxic
Fred Baxter MD CCFPFRCPC, Shock Syndrome
Jim McChesney MB CHB FRCPC
Purpose: To review the literature on group A streptococcal toxic shock syndrome, (STSS).
Data source: Medline and EMBASE searches were conducted using the key words group A streptococcal toxic
shock syndrome, alone and in combination with anesthesia; and septic shock, combined with anesthesia. Medline
was also searched using key words intravenous immunoglobulin, (IVIG) and group A streptococcus, (GAS); and
group A streptococcus and antibiotic therapy. Other references were included in this review if they addressed the
history, microbiology, pathophysiology, incidence, mortality, presentation and management of invasive GAS infec-
tions. Relevant references from the papers reviewed were also considered. Articles on the foregoing topics were
included regardless of study design. Non-English language studies were excluded. Literature on the efficacy of IVIG
and optimal antibiotic therapy was specifically searched.
Principal findings: Reports of invasive GAS infections have recently increased. Invasive GAS infection is associ-
ated with a toxic shock syndrome, (STSS), in 8 - 14% of cases. The STSS characteristically results in shock and
multi-organ failure soon after the onset of symptoms, and is associated with a mortality of 33 - 81%. Many of
these patients will require extensive soft tissue debridement or amputation in the operating room, on an emer-
gency basis. The extent of tissue debridement required is often underestimated before skin incision.
Conclusions: Management of STSS requires volume resuscitation, vasopressor/inotrope infusion, antibiotic ther-
apy and supportive care in an intensive care unit, usually including mechanical ventilation. Intravenous
immunoglobulin infusion has been recommended. Further studies are needed to define the role of IVIG in STSS
management and to determine optimal anesthetic management of patients with septic shock.
Objectif : Passer en revue la documentation sur le syndrome de choc toxique streptococcique de groupe A
(SCTS).
Sources : Des recherches ont été menées dans Medline et EMBASE en utilisant les mots-clés: group A strepto-
coccal toxic shock syndrome, seul et en combinaison avec anesthesia; septicshock, combiné avec anesthesia. Dans
Medline, nous avons aussi utilisé les entrées intravenousimmunoglobulin (immunoblobuline intraveineuse, IGIV) et
group A streptococcus (streptocoque du groupe A, SGA) et antibiotic therapy. Nous avons retenu d’autres
références qui concernaient l’histoire, la microbiologie, la physiopathologie, l’incidence, la mortalité, la présenta-
tion et le traitement des infections invasives de SGA. Les références pertinentes provenant des articles révisés ont
aussi été conservées. Les articles concernant les sujets déjà cités ont été retenus sans tenir compte du type d’é-
tude. On a exclu les études d’autres langues que l’anglais. La documentation sur l’efficacité de l’IGIV et sur l’an-
tibiothérapie optimale a été spécialement recherchée.
Constatations principales : Les articles sur les infections envahissantes de SGA ont récemment augmenté.
L’infection invasive de SGA est associée au syndrome de choc toxique (SCTS) dans 13-14 % des cas. Le SCTS
cause, de façon caractéristique, un choc et une défaillance multiorganique peu après l’apparition des symptômes.
Il s’accompagne d’un taux de mortalité de 33-81 %. Nombre des patients atteints auront besoin, de manière
urgente, d’un débridement considérable du tissu mou ou d’une amputation. L’étendue du débridement tissulaire
requis est souvent sous-estimée avant l’incision cutanée.
Conclusion : Le traitement du SCTS exige la restauration de la masse sanguine, des perfusions de vaso-
presseurs/inotropes, une antibiothérapie et des soins de soutien, incluant habituellement une ventilation
mécanique, à l’unité des soins intensifs. La perfusion intraveineuse d’immunoglobuline est recommandée.
D’autres études sont nécessaires pour définir le rôle de l’IGIV dans le traitement du SCTS et déterminer la ligne
de conduite anesthésique la plus avantageuse pour les patients en choc septique.
From the Departments of Anaesthesiology and Critical Care, McMaster University, St. Joseph’s Hospital, 50 Charlton Ave. E, Hamilton,
Ontario, Canada, L8N4A6.
Address correspondence to: Dr. F. Baxter. Fax: [phone]; E-mail: [email protected].
Accepted for publication August 15, 2000.
CAN J ANESTH 2000 / 47: 11 / pp 1129–1140
1130 CANADIANJOURNAL OF ANESTHESIA
T
HE past decade has witnessed the resur- History of GAS Infection
gence of the group A streptococcus as a Streptococcal infection, in the form of scarlet fever,
lethal pathogen.1,2 A syndrome of septic has been described since antiquity.15 Epidemics of
shock and multiorgan failure, affecting both benign and fatal disease were reported, including
both children and adults, has been associated with an epidemic in the American Colonies in 1736, which
severe, invasive and, less commonly, non-invasive GAS resulted in the death of 4000 people.15,16In the 19th
infection.2–11 This syndrome, reminiscent of the century, the lethality of GAS infection dramatically
staphylococcal toxic shock syndrome,2,12 has been increased in both Europe and North America. Scarlet
labelled the streptococcal toxic shock syndrome, with fever became the most common fatal infectious disease
diagnostic criteria defined.12,13 of childhood.15
Although apparently increasing in frequency, STSS After 1900, scarlet fever again became a more
is seen relatively uncommonly in most emergency benign disease although epidemics of rheumatic fever
departments and intensive care units. It is, therefore, remained a problem in the military during World War
important to have a high index of suspicion for this II17and post-streptococcal glomerulonephritis18was
condition. Patients with necrotizing fasciitis and strep- reported in several locations in the United States.
tococcal myositis require emergency debridement in Puerperal sepsis caused by GAS and streptococcal bac-
the operating room, thereby involving anesthesiolo- teremia were also reported.19,20 A case series of 20
gists in their care. The emergency nature of these patients with streptococcal necrotizing fasciitis was
cases, the degree of hemodynamic and respiratory published in 1920.21
instability associated with STSS and the need for mas- From the early 1950s until 1987, reported cases of
sive tissue debridement, make these cases challenging severe GAS infections became less common, although
for the anesthesiologist and the intensivist. case series of patients with severe and often fatal GAS
infections, associated with shock, were reported in the
Methods 1960s, 70s and 80s.22–26In 1987, Cone described two
References were included if they addressed the history, patients with invasive GAS soft tissue infection associ-
microbiology, pathophysiology, epidemiology, mortali- ated with a toxic shock-like syndrome.2Subsequently
ty, clinical presentation and management of invasive a case series of 20 patients with severe GAS infection
group A streptococcal infections or toxic shock syn- and a toxic shock-like syndrome was reported, associ-
drome. Medline and EMBASE searches were conduct- ated with a 30% mortality.1
ed using key words: group A streptococcal toxic shock Since 1987, there has been an increase in virulent
syndrome, alone and in combination with anesthesia; streptococcal disease reported worldwide. A consen-
and septic shock combined with anesthesia. sus statement on the case definition of STSS has been
Medline was searched using key words intravenous published (Table I).12
immunoglobulin and group A streptococcus; and
group A streptococcus with antibiotic therapy; intra-
venous immunoglobulin and toxic shock syndrome;
intravenous immunoglobulin and sepsis or septic
shock; and necrotizing fasciitis. Further references
were obtained from the bibliographies of the papers TABLE I Case definition of Group A Streptococcal Toxic Shock
Syndrome
which were reviewed.
Levels of evidence, as a guide to grading recom- 1) Isolation of GAS
mendations for therapy, were applied.14Grade A rec- 2) Clinical signs of severity:
a) Hypotension: Adult- Systolic BP #90mm Hg
ommendations are made when supportive evidence is
Child- #5th percentile for age
derived from randomized controlled trials, (RCTs), or
AND
meta-analysis of RCTs where the lower limit of the b) $ 2 of the following signs:
confidence intervals exceeds the minimally important -renal impairment
clinical benefit. Grade B recommendations may be -coagulopathy - platelets <100,00·mm–3
- DIC
derived from a single randomized trial or meta-analy-
-liver involvement - elevated AST, ALT,
sis of RCTs where results are disparate or consistent
Bilirubin
but treatment effects overlap the minimally clinically -Adult Respiratory Distress Syndrome
important benefit. Grade C recommendations result -generalized erythematous macular rash -
from non-randomized, concurrent cohort studies, his- may desquamate
toric cohort studies or case series.14 -soft tissue necrosis
Baxter & McChesney: STREPTOCOCCAL INFECTION 1131
Microbiology TABLE II Risk Factors For Invasive Group A Streptococcal
The group A streptococcus is a gram positive organ- Infection
ism, classified by the presence of surface proteins, pri-
Age < 9 yr or > 60 yr33,34
marily M and T antigens. More than 90 M protein Race: Native American,34African American36
serotypes have been identified. Varicella33,36
The M protein is the primary factor responsible for HIV/AIDS33,36
Cancer33
resistance to phagocytosis, thus determining the
Diabetes33,36
degree of virulence of the organism.27 M protein
Heart Disease33
diminishes complement activation by the alternate Lung Disease33
pathway, thereby inhibiting C3 deposition on the bac- Alcohol Abuse33
terial cell, thus increasing resistance to complement Nursing Home36
and phagocytosis. Streptococcal strains that are encap-
sulated and rich in M protein are more virulent.27
Homologous M antibodies afford protection to the
host from invasive streptococcal infection but do not infection with GAS has been raised.40,41Possible mech-
prevent the carrier state.27Most of the strains respon- anisms include 1) attenuation of signs and symptoms of
sible for STSS have been M protein types 1 and 3 but local infection, causing delay in diagnosis; 2) suppres-
other strains have also been identified.28 sion of granulocyte function; 3) enhanced production
Extracellular products of GAS include the of cytokines.40–42 Nonsteroidal antiinflammatory use
hemolysins streptolysin O and streptolysin S, strepto- prior to diagnosis was associated with a relative risk of
coccal pyrogenic exotoxins, (SPE), A, B and C, and mortality of 3.25, CI 1.16 - 8.7; P = .015 in one pop-
streptococcal superantigen. The streptococcal exotox- ulation based study.36It is unclear whether this rela-
ins possess superantigenic properties, which trigger tionship represents a causative effect or an association
massive T cell proliferation and cytokine release and with more severe disease.36Ibuprofen use was associat-
are thought to be the major pathogenic factor in STSS ed with necrotizing fasciitis in a case-control study of
initiation.29–31 Other GAS superantigens, which have pediatric patients with varicella.42
not yet been identified, may also contribute to the Severe GAS infections presented in the form of
development of the STSS.32 necrotizing fasciitis, myositis or cellulitis in 48 - 55%
of cases.33,35–6Most cases of invasive GAS infection are
Incidence and mortality community acquired. However, a recent population -
Population based studies in Canada and the U.S. have based study found that 14% of 323 cases were noso-
documented an incidence of invasive GAS infection of comial.33
1.5 - 5.2 cases/100,000 population annually. Eight to
14% of patients who develop invasive GAS infection Pathophysiology
will also develop STSS. Mortality associated with Septic shock is a syndrome triggered by infection
STSS ranged from 33 - 81% in four population - based which results in the production and release of endoge-
studies.33–36 nous mediators from monocytes, macrophages, neu-
Severe GAS infections may present in any age group, trophils and endothelium. These mediators induce a
including the neonate,37although the incidence is high- clinical state of vasodilation, myocardial depression,
est in the elderly and the very young.33–36Elderly nurs- capillary leak, immune suppression and organ fail-
ing home residents are at greater risk of severe GAS ure.43–45 Gram positive and gram negative organisms
disease compared with elderly people living in the com- produce a similar clinical picture although the bacter-
munity.36Healthy, young, immunocompetent children ial products triggering the syndrome are different.46–47
and adults are frequently infected although a higher The STSS is thought to be mediated by the release
incidence has been reported in patients with HIV, can- of SPEs and other antigens, which function as super-
cer, diabetes, ethanol abuse or other chronic dis- antigens.29–32 Superantigens stimulate T cells in a
eases33–36 (Table II). Patients with a recent history of manner which bypasses classical antigen processing
varicella (chickenpox) are at a markedly increased risk of mechanisms, by binding simultaneously with the Vß
infection with GAS, (62.7·100,000–1cases of varicel- region of the T cell receptor and the class II major his-
la·yr–1),33–36, 38and are frequently misdiagnosed on the tocompatibility complex of the antigen presenting
initial visit, thus delaying treatment.39 cell. This results in excessive T cell proliferation with
The possibility that the use of nonsteroidal anti- massive cytokine production, resulting in the
inflammatory drugs, (NSAID), may mask or enhance STSS.29–32,46,48 A peptide which blocks the lethal
1132 CANADIANJOURNAL OF ANESTHESIA
effects of staphylococcal and streptococcal superanti- Clinical presentation
gens in mice has recently been synthesized.49 Table III lists reported sites of infection with GAS.
Streptococcal pyrogenic exotoxin A and strep- a) Soft Tissue Infection
tolysin O have been shown to induce human mono- Necrotizing fasciitis is an infection of the subcuta-
cytes to produce tumour necrosis factor a neous tissue, destroying the fascia and fat and often
(TNF-a )50,51and interleukin-1ß (II - 1ß)51in vitro. In sparing the skin until late in the course of infec-
a baboon model of STSS, TNF-a production was tion.58,59A case of necrotizing fasciitis of the retroperi-
found to be increased.52Mortality was improved by toneum has been reported.60The extent of infection is
administration of anti-TNF antibody.41These studies often not appreciated as the skin findings may be min-
suggest that TNF-a plays a role in the pathogenesis of imal compared with the extent of subcutaneous tissue
STSS. destruction.41,58,61–64A delay in diagnosis is common9
It is unclear why there has been a recent worldwide and is associated with increased mortality.65,66 Severe
increase in reports of severe GAS infections.53–55 It is pain, often of sudden onset and out of proportion to
likely that both host factors, in terms of immunity, and the superficial appearance of the skin, is characteristic
bacterial factors are involved.53,54 of invasive GAS soft tissue infection and should raise
Host factors probably play a role in the severity of this as a diagnostic possibility.9,11,58,61–63,67
infection, as it has been demonstrated that the same Skin signs of necrotizing fasciitis include diffuse
strain of GAS may cause severe invasive disease, mild swelling and tenderness, a peau d’orange appearance,
uncomplicated disease, or be present in a carrier state.53 erythema, and later, the formation of bullae. Later still,
In a study assessing the role that protective humoral the skin colour changes from red to purple or black,
immunity plays in the development of severe GAS when the skin becomes necrotic. (Figure). The skin
infection, it was demonstrated that antibody levels to may become anesthetized as a result of nerve damage.9
specific M protein and to the streptococcal superanti- Infection may occur spontaneously, may follow
gens were lower in patients with invasive streptococcal very minor trauma or varicella infection, or may pre-
infections than in healthy controls.53 The levels of anti- sent as a surgical wound infection.64A high fever is
streptococcal superantigen neutralizing antibodies were commonly present.1
not different in patients with severe disease (STSS or A recent increase in the incidence of necrotizing
necrotizing fasciitis) compared with patients with inva- fasciitis, from 0.085·100000–1·yr–1 in 1991-1992 to
sive non-severe disease (bacteremia, cellulitis or 0.4·100000–1·yr–1in 1994-1995 has been document-
erysipelas). These findings suggest that the presence of ed in Ontario.68In a population based prospective sur-
specific anti-M antibody confers upon the host protec- veillance of cases in Ontario, both incidence and
tion from infection with that strain of GAS but, once mortality increased with age.68 Mortality was also
infected, antistreptococcal superantigen antibodies do associated with the presence of bacteremia and
not confer protection from STSS.53The authors postu-
lated that other host factors may determine the pres-
ence or absence of shock and organ failure.53
TABLE III Reported site of infection
Bacterial factors have also probably played a role in
Soft tissue - cellulitis, necrotizing fasciitis, myositis
the recent increase in incidence of severe GAS infec-
Pneumonia/empyema
tions. Despite the fact that invasive GAS infection and
Bacteremia - source unidentified
STSS have been associated with multiple strains of Surgical site infection
GAS,56,57a change in the prevalence of organisms with Septic arthritis
specific virulence factors may, in part, be responsible Thrombophlebitis (ivdrug abusers)
for the increased severity of GAS infection.54 One Meningitis
Peritonitis
study has shown a strong association between infec-
Retroperitoneal necrotizing fasciitis
tion with strains possessing the SPEA gene and Central venous catheter related bacteremia
STSS.55 These authors also documented two epidemic Pelvic infection
waves of genetically homogeneous T1M1 isolates Puerperal sepsis
associated with an increased risk of STSS.55Kaplan has Endocarditis
Otitis media
postulated that virulence factors such as phage DNA
Endophthalmitis
may be transmitted to different GAS serotypes, thus Osteomyelitis
explaining the serotypic diversity of isolates of GAS Cerebral empyema
from patients with invasive infection.54 Urinary tract infection
Upper respiratory tract infection
Baxter & McChesney: STREPTOCOCCAL INFECTION 1133
is controversial. It should never delay surgical debride-
ment.58,62,63,72
b) Pneumonia
Pneumonia caused by GAS presents as a rapidly pro-
gressive community acquired bronchopneumonia,
often associated with a preceding viral infection.28
Mortality was 33% in one study.33Nosocomial pneu-
monia with GAS has also been reported.36
c) Bacteremia
Group A streptococcal bacteremia may present with
no obvious focus of infection.33–36A thorough search
of the skin and soft tissues, as well as the usual diag-
nostic investigations for sepsis should be carried out
FIGURESevere, advanced necrotizing fasciitis of the face. The
and repeated until a source of infection has been iden-
patient was previously healthy, had been symptomatic for less than
72 hr, and presented in septic shock and renal failure. tified. Mortality of bacteremia without a septic focus
was 24-26%.33–35 Intravenous drug abuse was com-
monly associated with bacteremia in the 14-40 yr age
group.61
hypotension.68Toxic shock syndrome was present in d) Streptococcal toxic shock syndrome
47% of cases.68 Criteria for diagnosis of the STSS have been defined
Myositis with GAS is associated with a very high (Table I).12Patients with STSS were older on average
mortality (80 -100%).62 Traumatic injury is not a nec- and more likely to have underlying chronic disease
essary prerequisite and hematogenous spread from than patients with invasive GAS without STSS.33
other sites of infection (eg pharyngitis) may provide a Nevertheless, numerous cases of STSS have been
source of infection.58,61 Severe pain with tenderness, reported in otherwise healthy children and young
swelling and overlying erythema is characteristic.58,61–63 adults.1,33–35
Cellulitis presents with pain, induration and erythe- A rapid onset of septic shock associated with early
ma of the skin.58 Differentiation of cellulitis from organ dysfunction, should raise the possibility of STSS
necrotizing fasciitis or myositis may be difficult on and precipitate a search for the site of infection. Severe
clinical grounds alone.9Pain out of proportion to the pain at the site of infection is common on presenta-
degree of skin involvement suggests underlying necro- tion.58,61,62 Fever and a flu-like syndrome with myal-
tizing fasciitis or myositis. Early differentiation of the gia, chills, nausea, vomiting and diarrhea are a
two conditions is critical as their management is very common prodrome. Confusion is frequently present.1
different. Failure to perform rapid, extensive surgical Hypotension is a presenting sign or develops shortly
debridement of necrotic tissue has been associated after presentation.58,62
with increased mortality66,69–71 and will result in Organ dysfunction may precede the onset of
increased tissue loss. In a prospective study of GAS hypotension in STSS.1,58 Laboratory studies often
necrotizing fasciitis in Ontario, all patients who did reveal a markedly elevated creatinine which frequently
not receive surgery, died.68 precedes the onset of hypotension.11,62 Dialysis was
Necrotizing fasciitis is a surgical emergency. required in 2-10% of patients with severe GAS infec-
Diagnosis should be made by surgical exploration, with tion.1,9,11Renal function usually returns to normal in
biopsy and frozen section if necessary.59,71Non-invasive survivors.1,11,73Hyperkalemia may be present and may
diagnosis with CT scan or Magnetic Resonance require urgent dialysis. Hypocalcemia, probably
Imaging delays surgical debridement, which may caused by elevated calcitonin levels,11hypoalbumine-
increase morbidity and mortality.59 Debridement of all mia and elevated liver transaminases are commonly
necrotic tissue, which may include amputation, should found at the time of admission. The granulocyte
be carried out on an emergency basis. Repeated, often count is usually elevated, with a marked left shift. In
daily, debridement is usually required.9,59 the presence of necrotizing fasciitis or myositis, crea-
Hyperbaric oxygen therapy has not been proved to tine phosphokinase, (CPK), levels are markedly elevat-
be of benefit in gram positive soft tissue infection and ed.63 Coagulopathy, with disseminated intravascular
1134 CANADIANJOURNAL OF ANESTHESIA
coagulation, (DIC), is frequently present on admis- of 56 children with invasive GAS demonstrated an
sion and two cases of purpura fulminans, associated improvement in the rate of progression of disease in
with STSS have been reported.63 patients treated with protein synthesis-inhibiting antibi-
Respiratory failure with ARDS required mechanical otics, (predominantly clindamycin), compared with
ventilation in 42-50% of patients with invasive GAS those receiving cell wall-inhibiting antibiotics (predom-
infections.1,11 The hemodynamic picture for patients inantly ß lactams).81A lower case-fatality rate associated
with STSS includes tachycardia and a decreased left with clindamycin use was documented in a population
ventricular stroke work index.68Hypotension is due to based survey of patients with GAS necrotizing fasciitis;
vasodilation, volume depletion and myocardial (relative risk 0.55, 95% confidence intervals 0.23-1.02,
depression. P= 0.06).68
The majority of patients, (69-97%), with severe Therefore, it is recommended that high dose peni-
GAS infection have positive blood cultures.33–36 cillin G, (24,000,000 units/day iv, in divided doses, if
Cultures from the site of infection, including tissue renal function is normal) and clindamycin, (600-900
taken at surgery, CSF, pleural fluid, or synovial fluid mg Q8H iv) be given if invasive GAS infection is sus-
are positive in 95% of cases.1 pected82 (Grade C). Antibiotic coverage for
Streptococcal toxic shock syndrome is most com- Staphylococcus aureus, gram negative and anaerobic
monly associated with necrotizing fasciitis and pneu- organisms should also be administered in cases of soft
monia,33 but may be associated with any invasive tissue infection until the pathogen is identified.58,63,72
infection or, less commonly, superficial or upper respi- Aminoglycosides should be used cautiously as renal
ratory infection.33–5 Bacteremia with no identified failure is common in STSS.
focus is also associated with STSS and a mortality rate The STSS is believed to be mediated by streptococ-
of 24-26%.33,35 cal exotoxins.29–32Commercial IVIG contains neutraliz-
ing antibody to streptococcal exotoxins.32,83,84 Several
Management case reports have described the use of IVIG in patients
The presence of necrotizing fasciitis or myositis man- with STSS,37,73,85–91 and a case control study of IVIG
dates immediate surgical debridement or amputation, therapy in STSS demonstrated a survival benefit in
and constitutes a surgical emergency.59,62,63,67–72,74The patients who received IVIG.92The recommended initial
infection spreads rapidly and is often much more dosage is 2 g·kg–1,82followed by 0.4 g·kg–1·day–1for up
extensive than appreciated from examination of the to five days. It should be given as soon as STSS is sus-
skin surface.41,58–61,63,64The spread of infection in the pected.93 Intravenous immunoglobulin is recommend-
wound may outpace the rate of surgical debride- ed only in patients with toxic shock syndrome. It is
ment.63Debridement of all infected tissue should be contraindicated in patients with IgA deficiency, circulat-
carried out at the first operative procedure.59Most ing anti-IgA antibodies, or a history of anaphylaxis asso-
patients require at least one return to the OR to ciated with immune globulin.72Its efficacy has yet to be
ensure that all infected tissue has been removed.59,65,71 proved in randomized controlled trials93(Grade C).
Resuscitation, stabilization and, on occasion, dialysis, Supportive management of patients with STSS will
may have to be carried out in the OR. frequently require tracheal intubation and mechanical
The group A streptococcus remains sensitive to peni- ventilation. In one descriptive study, survivors of inva-
cillin. However, a reduction in the efficacy of penicillin sive GAS infections required a mean of 18 days venti-
when a high density of organisms is present has been lator support.63 Invasive monitoring is indicated.
demonstrated.58This reduction in efficacy may be relat- Principles of management of septic shock have been
ed to a decrease in the expression of penicillin binding published elsewhere.94–96
proteins by the organisms in the stationary phase of Volume deficits are often massive due to external
growth.75 Large inoculums of organisms, as found in and interstitial fluid loss, combined with peripheral
severe GAS infections, reach the stationary phase of vasodilation and venous pooling. Vasopressor therapy
growth more quickly, making penicillin less effective. is usually required. Recent data suggests that norepi-
Clindamycin acts by inhibiting protein synthesis. Its nephrine combined with dobutamine, may be a better
action and efficacy is not affected by the stage of choice than either high dose dopamine or epineph-
growth. It has been proposed that clindamycin may also rine, to maintain splanchnic perfusion97–99 (Grade B).
confer benefit by inhibiting the synthesis of bacterial Volume status should be optimized during vasopres-
toxins, M protein and TNF-a .76–79In a murine model sor therapy to avoid masking a volume deficit with
of severe GAS infection, clindamycin was found to be vasopressors. A pulmonary artery catheter may be
more effective than penicillin.80A retrospective review helpful in this regard. Frequent ongoing assessment of
Baxter & McChesney: STREPTOCOCCAL INFECTION 1135
clinical parameters of organ perfusion such as urine a lifesaving procedure.62,63,67,68,72 There is often little
output, acid-base status, lactate levels, mentation and time for assessment and stabilization of the patient
ST segment changes should be carried out. before transfer to the OR. The rapidity with which tissue
The use of corticosteroids in septic shock remains loss occurs with invasive GAS infection makes rapid
controversial. Early, high dose steroid therapy has not resuscitation and stabilization, to the degree necessary to
been shown to be effective in sepsis in a meta-analysis allow induction of anesthesia, a priority.
of eight randomized trials100 (Grade A). Two recent The extent of necessary debridement is often gross-
studies suggest that reversal of the hemodynamic ly underestimated before the incision is made.41,58,61–3
sequelae of late septic shock may be enhanced by low Therefore, the anesthesiologist is frequently presented
dose steroid supplementation101,102(Grade B). If there with a hemodynamically unstable patient with multi-
is any doubt of the adequacy of adrenal function, an system failure, severe coagulopathy and impending
empirical dose of dexamethasone, (4 mg Q6H iv), respiratory failure.1,74The patient is potentially facing
may be given, pending the performance of an ACTH a long surgical procedure with extensive blood loss,
stimulation test.95 and must be triaged for the operating room on an
Renal failure occurs early in the course of STSS.1 emergency basis.
Serum potassium must be monitored carefully and Adequate blood products, including platelets, must
dialysis may be required. Rhabdomyolysis may occur be readily available. Intravenous immunoglobulin and
in necrotizing fasciitis or myositis. Urine myoglobin antibiotic therapy should be continued intraoperative-
may be negative initially and should be repeatedly test- ly. Large bore iv access and arterial line monitoring
ed. DIC may be present. Rapid correction of coagula- should be obtained. Vasopressor therapy should be
tion abnormalities with blood products must be available for intraoperative use.The need for rapid vol-
carried out to allow surgical debridement of infected ume resuscitation should be anticipated since the
tissue to proceed. speed of surgical debridement may not allow for
prompt hemostasis. A central venous or pulmonary
Prophylaxis artery catheter should be considered, bearing in mind
It has been estimated, based on a population based that a coagulopathy may exist.63 Hypocalcemia is
study in Ontario, that the incidence of invasive GAS common in STSS, may be present preoperatively and
infection among members of the patient’s household may be exacerbated by the rapid infusion of blood
is nearly 200 times higher than the risk to the general products. Hyperkalemia may be present if renal failure
population.33 However, in a recent statement on is a feature and may require medical management or
chemoprophylaxis for household contacts of patients even dialysis while the patient is in the OR. If the need
with invasive GAS infection, the Working Group for for dialysis is anticipated preoperatively, it may be pru-
the Centres for Disease Control and Prevention con- dent to insert an appropriate dialysis catheter when a
cluded that no definitive recommendations could be central vein is cannulated.
made. They suggested that each case be dealt with on Sepsis and shock may result in gastrointestinal
the basis of the clinicians assessment of the risk to the mucosal ischemia.106Dysfunction of the gastrointesti-
contact.65Other authors have recommended prophy- nal tract should be anticipated. The patient should be
laxis.72Although optimal antibiotic regimens have not managed as if a full stomach is present. A nasogastric
yet been formulated, a 10 day course of cephalosporin tube should be considered.
or a macrolide has been proposed72 (Grade C). There is no specific technique which has been
Nosocomial transmission of GAS and transmission demonstrated to be superior for the induction of anes-
of GAS from patients to health care workers has been thesia in the patient with septic shock.108If the patient
documented.35,36,103–5 Appropriate precautions, is hemodynamically unstable or in impending respira-
including gown, mask, gloves and meticulous hand- tory failure, awake tracheal intubation may be consid-
washing should be instituted to protect other patients ered. This can be followed by a gradual induction of
as well as those caring for the patient.105 anesthesia, attempting to maintain hemodynamic sta-
bility. Drugs or anesthetic agents causing vasodilata-
Anesthesia for Patients With Severe GAS Infection tion or myocardial depression should be avoided or
and STSS used with caution. An animal model suggests that the
Patients with invasive GAS infection usually come to MAC of isoflurane is decreased in sepsis.108A compar-
surgery for debridement of extensive soft tissue infec- ison of halothane, isoflurane, alfentanil and ketamine
tions. The presence of necrotizing fasciitis or streptococ- in a dog model of septic shock demonstrated better
cal myositis mandates immediate surgical debridement as preservation of cardiovascular stability with ketamine
1136 CANADIANJOURNAL OF ANESTHESIA
than with other agents.109Ketamine has been shown 7 Wheeler MC, Roe MH, Kaplan EL, Schlievert PM,
to preserve sympathetic drive despite its intrinsic Todd JK.Outbreaks of group A streptococcus sep-
myocardial depressant properties110and may be a rea- ticemia in children. Clinical, epidemiologic, and
sonable choice. Other agents have also been used microbiological correlates. JAMA 1991; 266: 533–7.
effectively.111 Neuraxial techniques are relatively con- 8 Soravia C, Romand J-A, Herrmann M, Chevrolet J-C,
traindicated in the septic patient, particularly if the Ricou B, Suter PM.Group A beta-haemolytic strepto-
patient is hemodynamically unstable. coccus septicemia: the toxic shock syndrome.
Tracheal intubation and mechanical ventilation are Intensive Care Med 1993; 19: 53–6.
required to allow for adequate alveolar ventilation in 9 Chelsom J, Halstensen A, Haga T, Høiby EA.
sepsis. Capnography should be used to guide minute Necrotizing fasciitis due to group A streptococci in
ventilation since carbon dioxide production may be western Norway: incidence and clinical features.
increased. Core temperature monitoring is essential Lancet 1994; 344: 1111–5.
since the pyrexia of sepsis may be countered by the 10 Drabick JJ, Lennox JL.Group A streptococcal infec-
extensive heat loss and evaporation from the debrided tions and a toxic shock - like syndrome (Letter). N
area. Intravenous fluid warmers and peripheral warming Engl J Med 1989; 321: 1545.
blankets may be useful for temperature homeostasis. 11 Demers B, Simor AE, Velland H,et al.Severe invasive
Intraoperative monitoring of CBC and platelet group A streptococcal infections in Ontario, Canada:
count, coagulation parameters, serum electrolytes, 1987 - 1991. Clin Infect Dis 1993; 16: 792–800.
including Ca++, renal function, arterial blood gases and 12 The Working Group on Severe Streptococcal
pH should be undertaken at frequent intervals. A uri- Infections. Defining the group A streptococcal toxic
nary catheter should be used to monitor urine output. shock syndrome: rationale and consensus definition.
The need for continued inotropic support and JAMA 1993; 269: 390–1.
mechanical ventilation into the postoperative period 13 Bartter T, Dascal A, Carroll K, Curley FJ.“Toxic
should be anticipated. The anesthesia team may be strep syndrome.” A manifestation of group A strepto-
involved in further operative debridement and pain coccal infection. Arch Intern Med 1988; 148:
management after surgery, which remains a challenge 1421–4.
during the recovery phase. 14 Cook DJ, Guyatt GH, Laupacis A, Sackett DL,
Goldberg RJ.Clinical recommendations using levels
Acknowledgement of evidence for antithrombotic agents. Chest 1995;
The authors wish to thank Dr. Deborah Cook for her 108: 227s–30.
excellent suggestions regarding the preparation of this 15 Katz AR, Morens DM. Severe streptococcal infections
manuscript. in historical perspective. Clin Infect Dis 1992; 14:
298–307.
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