Keywords central extracorporeal membrane oxygenation - extracorporeal carbon dioxide removal
- group A β-hemolytic
Streptococcus
- intensive care unit - outcomes - pediatric - septic shock
Introduction
A previously healthy 4-year, 10-month old boy (18 kg) was seen by his pediatrician
for a fever to 101°F and an overnight “barky cough.” He received an oral dose of dexamethasone
and was discharged home. Later that afternoon, he developed increased respiratory
distress and was evaluated in an outside hospital. He received a 20-mL/kg normal saline
intravenous (IV) bolus, a racemic epinephrine nebulization, and IV dexamethasone.
Due to concerns of impending respiratory failure, he was transferred to a higher level
of care facility.
Upon arrival of the transport team, he was breathing at a rate of 60 breaths/min while
receiving 15 L/min of oxygen via a nonrebreathing facemask. He was restless, but warm
and well perfused with strong pulses. His breathing increased during transport and
he was placed on continuous positive airway pressure at 10 cm H2 O. Despite maximal medical interventions, he required immediate intubation and mechanical
ventilation due to hypoxemic respiratory failure when he arrived to the pediatric
intensive care unit (PICU).
Later in the evening, he was found to have anisocoria and was given hypertonic (3%)
saline. An emergent head computed tomography scan (CT scan) was normal. Approximately
17 hours after admission, an arterial blood gas demonstrated a pH of 7.19, PaCO2 of 50 mm Hg, PaO2 of 85 mm Hg, and a base deficit of −9.1. He was receiving conventional mechanical
ventilation in the pressure-regulated volume control modality with a tidal volume
of 6 mL/kg, positive end-expiratory pressure of 14 cm H2 O, rate of 30, and FiO2 of 70% while in the prone position. His peak inspiratory pressure (PIP) was 33 cm
H2 O. Due to hemodynamic instability, patient continued to receive large crystalloid
and colloid volume resuscitation. His net fluid balance at this point was close to
2.7 positive. His chest X-ray revealed patchy peripheral and bilateral lower lobe
opacities with left pleural effusion ([Fig. 1A ]). Given his worsening metabolic acidosis, increasing pulmonary edema, and elevated
central venous pressure, an echocardiogram was ordered to assess his cardiac function.
He was noted to have good systolic function but diastolic dysfunction. Milrinone was
initiated at a continuous IV rate of 0.3 µg/kg/h. A complete blood count demonstrated
a white blood cell count of 660 cells/mm3 (64% lymphocytes, 24% segmented neutrophils, 188 absolute neutrophil count, and 422
absolute lymphocyte count). Polymerase chain reaction analysis for respiratory syncytial
virus from a nasopharyngeal secretion sample was positive. His throat and blood cultures
grew group A Streptococcus (GAS) bacteria approximately 19 hours after admission. He was treated empirically
with cefotaxime and clindamycin. He also received IV immunoglobulin G (IVIG) and plasmapheresis.
Fig. 1 (A ) CXR on the day of admission. Patchy peripheral and lower lobe opacities (left greater
than right). (B ) CXR the next evening revealing a large right-sided pneumothorax with lung collapse
along with probable mild to moderate left-sided pleural effusion. (C ) CXR postright chest tube placement. (D ) CXR postcardiac arrest a few hours later. Bilateral haziness consistent with pulmonary
edema. Persistence of mild to moderate left-sided pleural effusion. CXR, chest X-ray.
The patient continued to require volume resuscitation and was treated with escalating
doses of continuous vasopressor infusions including dopamine 20 µg/kg/min, epinephrine
0.2 µg/kg/min, norepinephrine 0.2 µg/kg/min, and milrinone 0.5 µg/kg/min. Vancomycin
was added to his antibiotic regimen. A repeat echocardiogram revealed diminished left
ventricular systolic function. Due to signs of inadequate oxygen delivery and hypoxemia,
inhaled nitric oxide was introduced at 20 ppm. During this time, he developed a right-sided
tension pneumothorax that was managed with a right-sided chest tube ([Fig. 1B ], [C ]). Despite these measures, his metabolic acidosis persisted and his lungs remained
poorly compliant with PIPs ranging from 45 to 50 cm H2 O. He went into cardiac arrest twice requiring cardiopulmonary resuscitation for approximately
2 and 15 minutes, respectively. His serum lactate levels continued to rise (up to
9 mmol/L) despite maximal medical support, thus the decision was made to electively
place him on peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO).
He was cannulated via his right internal jugular vein with a 22-French catheter and
his right carotid artery with a 16-French catheter. Shortly after peripheral VA ECMO
initiation, his heart went into asystole and his lung fields appeared to have near
total opacification ([Fig. 2B ]). He developed anasarca and exhibited intermittent anisocoria. Over the following
22 hours, his venous return progressively worsened despite aggressive fluid administration
and inotropic support. In addition, he became anuric and developed abdominal compartment
syndrome, and at this point, his net fluid balance was more than 5 L positive.
Fig. 2 (A ) CXR after initial cardiac arrest. Increasing pulmonary edema. (B ) CXR postECMO cannulation. Bilateral pulmonary edema. Increased right-sided emphysema.
Decreased pneumothorax. Left-sided mild to moderate pleural effusion. (C ) CXR approximately 6 weeks on ECMO. ECMO cannulas present. Bibasilar atelectasis
with bilateral pleural effusions. (D ) CXR 9.5 months after admission. Residual left lower lobe opacity with possible scarring
noted in the right upper lobe and left lower lobe regions. Blunting of both costophrenic
sulci with possible chronic small bilateral pleural effusions. CXR, chest X-ray; ECMO,
extracorporeal membrane oxygenation.
Thus, his peripheral VA ECMO support was converted to open chest central VA ECMO support
via a median sternotomy with the addition of a 24-French venous catheter to his right
atrium. In addition, his left atrium was vented with a 13-French catheter. The 16-French
arterial catheter was left in the right carotid artery. His heart was observed to
be markedly enlarged. Significant bilateral pleural effusions were drained directly
via his sternotomy incision. Two chest tubes and a mediastinal drain were placed and
the sternotomy was covered with a Silastic membrane. A Tenckhoff peritoneal catheter
was also placed after a significant amount of ascites was surgically drained. After
the addition of transthoracic cannulas, he had rapid and substantial improvement in
his ECMO flows increasing from 67 to 88 mL/kg/min in peripheral ECMO to 150 to 200
mL/kg/min after central cannulation (patient's dry weight was 18 kg at admission).
His lactic acidosis improved as well. Over the following week, his cardiac function
improved. On day 8 of VA ECMO, his transthoracic cannulas were removed, and he was
transitioned back to full support via his right neck vessels (peripheral VA ECMO).
Patient received continuous renal replacement therapy while on central ECMO, his kidney
function started to improve gradually, and he required slow continuous ultrafiltration
for fluid removal intermittently through his course.
Approximately 1 month into his VA ECMO support, he developed septic shock secondary
to Hemophilus influenzae that was isolated from his blood, respiratory secretions, and pericardial fluid.
He experienced significant bleeding from his mediastinum. Efforts were made to minimize
his anticoagulation by maintaining antifactor Xa levels in the range of 0.3 to 0.4
while normalizing his prothrombin time and platelet levels (goal of > 100,000/µL).
His antibiotic regiment of cefepime and meropenem was simplified to ceftriaxone to
target GAS and H. influenzae .
On day 37 of VA ECMO, mediastinal debridement was performed due to concerns that he
had developed mediastinitis. At this time, he was found to have a bronchopleural fistula
originating from his right lung. The area was packed with a kaolin impregnated sterile
gauze (QuickClot). To limit the positive pressure reaching his right lung and the
fistula to heal, the otolaryngology service performed bronchoscopy and placed his
endotracheal tube in the left main bronchus. After 2 days, mediastinal re-exploration
was performed and the kaolin impregnated sterile gauze was removed with no resulting
air leak. After 7 days, the endotracheal tube was pulled back to its typical position
above the carina. His mediastinum was gradually closed over the course of several
weeks.
Multiple efforts to wean him off of VA ECMO support and transitioning to VV ECMO were
unsuccessful because of severe respiratory acidosis even and the liable hemodynamic
status. On day 59 of VA ECMO support, he was transitioned to pumpless extracorporeal
CO2 removal (ECCO2 R) by placing a 14-French cannula in both his left femoral artery and left femoral
vein. His peripheral (right neck) ECMO cannulas were removed at that time. Over a
few weeks, his ECCO2 R support was gradually weaned. He was decannulated from ECCO2 R on day 75 of total extracorporeal support.
While on ECMO, patient was on Rotaflow ECMO system. While he was on VA ECMO, flow
range was 2 to 3.5 L/min, sweep varied greatly depending on age of oxygenator, his
sweep range between 2.5 and 8 L/min with higher sweep resulting in frequent oxygenator
changes for clotting and poor gases. FiO2 range between 50 and 100% for majority of his run up until ECCO2 R.
While on ECCO2 R, patient was on Rotaflow ECMO system. He started on pediatric Quadrox oxygenator,
but was changed to adult Quadrox within 12 hours to achieve higher flow rate. He remained
on adult Quadrox for the remainder of his ECCO2 R. ECCO2 R flow ranged between 0.4 and 0.5 L/min. Sweep rate ranged between 2 and 3 L/min at
21% FiO2 .
Heparin was used for anticoagulation with activated clotting time (ACT) goal of 160
to 180. Due to bleeding complications from chest, ACT range was lowered to 140 to
160 for majority of treatment. Heparin infusion was often at variable doses between
40 and 50 units/kg/h.
After 4.5 months of hospitalization, tracheostomy and gastrostomy tubes were placed.
On day 167 of hospitalization, efforts to sprint him off of the ventilator to a tracheostomy
collar began. The patient was discharged from the hospital requiring night time ventilation
through the tracheostomy tube. Overall, he spent 229 days in the hospital, 152 days
in the PICU and 77 days in the rehabilitation unit. At the time of his discharge,
the only neurological deficit that he exhibited was poor fine motor skills in his
hands for which he continued to receive physical therapy. He was discharged home on
amlodipine for systemic hypertension, sildenafil for pulmonary hypertension, albuterol,
and ipratropium.
Gradually, he was successfully weaned off of the ventilator and supplemental oxygen
over a period of 6 months. He tolerated the capping of his tracheostomy tube throughout
the day. He experienced shortness of breath while running, but he was able to engage
in normal activity without any significant respiratory problems. Fourteen months after
his original admission, spirometry revealed low vital capacity at 59% (0.84 L) of
predicted value for his age; nose clips and Microfoam tape around the tracheostomy
were used to minimize air leak during testing. These observations were consistent
with restrictive lung disease. A polysomnogram was performed with the tracheostomy
tube capped and demonstrated normal oxygenation and ventilation.
A follow-up chest radiograph revealed minor residual atelectasis in the left lower
lobe with small bilateral chronic pleural effusions ([Fig. 2D ]). A chest CT scan demonstrated traction bronchiectasis, atelectasis, and consolidation
of bilateral lower lung lobes greater on the left compared with the right ([Fig. 3 ]). Serial echocardiograms did not show any evidence of pulmonary artery hypertension;
therefore, sildenafil was successfully weaned off.
Fig. 3 CT scan of the chest 6.5 months after admission. Interval improved aeration of the
right lung and in the left upper lobe. Persistent atelectasis, fibrotic scarring of
the left lower lobe resulted with increasing cystic areas, and bronchiectasis changes.
Diffuse peribronchial thickening in bilateral peripheral region with extension of
fibrotic changes persist. (A ) Section of CT scan depicting lung apices above the carina. (B ) Section of CT scan near divergence of the main stem bronchi. (C ) Section of the CT scan just above the diaphragm. CT, computed tomography.
Discussion
Streptococcus pyogenes is a β-hemolytic bacterium that is also known as GAS. Invasive GAS accounts for 8,950
to 11,500 cases and 1,050 to 1,850 deaths each year in the United States.[1 ] The rates of disease are highest among children who are younger than 1 year of age
and persons older than 65 years of age.[1 ] GAS is responsible for a spectrum of illnesses in children, ranging from pharyngitis
to fatal invasive disease,[2 ]
[3 ] and it is an emerging cause of severe sepsis in children.[4 ]
In one case series from Melbourne over a 3-year period, 12 cases of invasive group
A streptococcal infection were admitted to the PICU.[4 ] The most common clinical presentations were pneumonia, bacteremia with no septic
focus, and septic arthritis. Fever and hypotension were common signs, but a rash was
infrequent. The typical patient had multiorgan dysfunction including some combination
of acute respiratory distress syndrome (ARDS), renal failure, liver dysfunction, and
coagulopathy.[4 ] Half of the patients required ECMO support ranging from 4 to 35 days though there
was no mention of which type of ECMO support, peripheral or central, was needed.[4 ]
Initial management of invasive GAS infections is centered on early antimicrobial therapy,
ensuring adequate cardiac output and supporting failing organs.[2 ] A two-pronged parenteral antimicrobial therapy strategy is recommended utilizing
a bactericidal agent (β-lactamase–resistant antimicrobial) and a protein synthesis
inhibiting agent (e.g., clindamycin) to diminish production of virulence factors.[5 ] IVIG should be considered for those refractory to escalating hemodynamic support
and meeting criteria for streptococcal toxic shock syndrome.[5 ]
[6 ]
The use of ECMO is part of the clinical practice parameters guidelines for hemodynamic
support of pediatric and neonatal septic shock.[7 ] The procedure is a form of cardiopulmonary bypass, modified for longer term support.
The patient's venous blood is emptied from the body via a large bore cannula, and
then, it is directed through a membrane oxygenator where carbon dioxide is removed
and oxygen is added before being returned into the venous or arterial circulation.[8 ] The typical insertion sites of the cannulas for peripheral ECMO include the large
vessels of the neck and/or groin. In central ECMO, the venous cannula is placed in
the inferior vena cava or right atrium (in a transthoracic approach), while the arterial
cannula is inserted into the ascending aorta by way of a median sternotomy. In general,
patients with isolated respiratory or cardiac failure are successfully supported using
ECMO flows that can be achieved using peripheral ECMO. Physical properties of the
length and diameter of the catheters and the size of the vascular bed being drained
play a role in the limitation of ECMO flow.[9 ] Our patient benefited from the higher flows achieved with central ECMO as well as
decompressing the tamponade caused by extensive pleural edema and effusion from disease
severity and fluid resuscitation.
We are certainly not the first institution to use central ECMO[10 ]
[11 ]
[12 ]
[13 ] for support of refractory septic shock, in either children[11 ]
[12 ]
[13 ]
[14 ] or adults.[15 ] MacLaren et al published a case series of children, many with overwhelming meningococcemia,
who had good outcomes utilizing central ECMO support in the setting of septic shock
by aiming to achieve “supernormal” ECMO flow to improve tissue bed perfusion, overcome
vasomotor paralysis, and resolve lactic acidosis.[14 ] While the successful use of central ECMO in septic shock has been reported, its
use in children still seems to be merely a consideration rather than an expectation.
At the time of this patient's presentation, we had extensive experience using peripheral
ECMO for support of septic shock, but often with disappointing results due to the
inability to achieve the desired supernormal ECMO flow. Our institution had extensive
experience with transthoracic ECMO support for cardiac failure, often postoperatively.
Given these experiences and the willingness of our cardiac surgical team to attempt
to support this patient with central ECMO, making the imaginative leap to put into
practice the lessons taught by our Australian colleagues was a relatively easy one.
In the largest Australian series reported using central ECMO support for refractory
septic shock, survival was statistically associated with maximal ECMO flow achieved
with survivors able to reach ECMO flows of 158 versus 111 mL/kg/min for nonsurvivors.[14 ] For our patient, ECMO flow increased from 67 to 88 mL/kg/min in peripheral ECMO
to 150 to 200 mL/kg/min after central cannulation. It should be noted that these ECMO
flows are approximately 50% higher than those typically recommended for venoarterial
support of either primary respiratory failure or primary cardiac failure.
The use of ECCO2 R to “bridge” our patient off VA ECMO support was a first for our institution, though
use of ECCO2 R for support of respiratory failure associated with severe hypercapnia is certainly
not novel, particularly in adult critical care medicine. ECCO2 R, also discussed in the literature as “low-flow ECMO,” may be performed in a venovenous
or an arteriovenous manner, analogous to continuous renal replacement therapy.[16 ] It allows use of ultraprotective ventilation strategies with very small tidal volumes
and transalveolar pressures.[16 ] Scattered case reports of the use of ECCO2 R in pediatric ARDS (PARDS) have been in existence since the early 1990s,[17 ] but given that the primary derangement in PARDS tends to be hypoxemia rather than
hypercapnia,[18 ]
[19 ]
[20 ] most pediatric respiratory ECMO support has traditionally used “high-flow” ECMO,
either venoarterial or venovenous.[8 ]
[10 ] Our patient's ARDS caused hypercapnia rather than hypoxemia off ECMO support, beside
the fact that the ECCO2 requires less anticoagulation and are associated with less complication; we were
encouraged to use it instead of VV ECMO as a bridge to wean our patient off of ECMO
support.
Conclusion
Group A streptococcal infection can present with a wide range of clinical symptoms
from fever and sore throat to severe life-threatening sepsis. Our patient's symptoms
evolved acutely and he remained hemodynamically unstable despite aggressive medical
management. Peripheral ECMO cannulation initially stabilized his condition, but then
his hemodynamics deteriorated with insufficient flow to meet his metabolic needs.
Central ECMO along with drainage of his pleural effusions and intraabdominal ascites
significantly improved his blood flow from 67 to 88 to 150 to 200 mL/kg/min.
After approximately 2 months on ECMO, he was transitioned to ECCO2 R due to refractory respiratory acidosis. He was completely decannulated approximately
2 weeks later with good neurological recovery. This experience suggests that consideration
should be given for the use of central ECMO in pediatric patients who remain hemodynamically
insufficient/unstable due to sepsis while on maximally optimized peripheral ECMO support.
Furthermore, ECCO2 R is a reasonable supportive option in children who exhibit persistent respiratory
acidosis while recovering from ARDS.
