Adult Respiratory Distress Syndrome in a Pediatric Intensive Care Unit: Predisposing Conditions, Clinical Course, and Outcome

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Adult

Respiratory

Distress

Syndrome

in a

Pediatric

Intensive

Care

Unit:

Predisposing

Conditions,

Clinical

Course,

and

Outcome

Raymond

K. Lyrene,

MD,

and

William

E. Truog,

MD

From the Department of Pediatrics, University of Washington School of Medicine, Seattle

ABSTRACT. Adult respiratory distress syndrome,

com-monly seen in adults, is not well recognized in children. A retrospective chart review was carried out to determine the relative incidence, predisposing conditions, clinical

course, and outcome of children with adult respiratory distress syndrome. Fifteen patients were identified. The

most common predisposing conditions were

near-drown-ing and near-strangulation with a noticeable absence of major trauma. Mortality was 60%. Death was most often

secondary to central nervous system complications. Air leak was the most common complication of treatment. Two of six survivors suffered major neurologic handicaps. Long-term pulmonary sequelae were minimal. Pediatrics

67:790-795, 1981; adult respiratory distress syndrome, pulmonary edema, shock lung, acute respiratory failure.

Adult

respiratory

distress

syndrome

(ARDS)

is a

clinical

entity

characterized

by

physical

signs

of

pulmonary

insufficiency,

impairment

in

gas

ex-change, decrease in lung compliance, and radio-graphic findings of diffuse pulmonary infiltrates.’3

Previous descriptions of ARDS in pediatric patients have been limited to case reports and inclusion of occasional children in published series of adult pa-tients. The present study was undertaken to ex-amine the occurrence of ARDS in a pediatric

inten-sive care

unit

and

to delineate

the

incidence,

pre-disposing factors, and mortality associated with this disease in children.

SUBJECTS

AND

METHODS

Patients included in this study were identified by

reviewing

all

admissions

to the

pediatric

intensive

Received for publication June 23, 1980; accepted Oct 15, 1980. Reprint requests to (R.K.L.) Division of Neonatal Biology, De-partment of Pediatrics, RD-20, RR-451 Health Sciences, Uni-versity of Washington School of Medicine, Seattle, WA 98195.

care unit at Children’s Orthopedic Hospital and

Medical Center, Seattle, for the 42-month period

from

January

1976

to July

1979.

Patients

selected

for inclusion

in this

study

were

more

than

6 months

of age,

had

an

acute

antecedent

illness

or

injury,

showed

a need

for mechanical

ventilation,

and

dem-onstrated

diffuse

bilateral

alveolar

infiltrates

on

chest radiograph. Records of all patients so

identi-fled

were

abstracted

for past

medical

history,

details

of the

predisposing

event,

evidence

of diffuse

lung

injury

by chest radiograph, reasons for instituting

ventilator

support,

and

management

of the

venti-lator, including peak inspiratory pressures and re-sponse to positive end-expiratory pressure (PEEP).

Effective

dynamic

compliance,

a measure

of total

respiratory

compliance,2

was

derived

from

the

res-piratory

care

records

by

dividing

delivered

tidal

volume

by the

difference

between

peak

inspiratory

pressure

and

end-expiratory

pressure

measured

at

the mouth. This value was then normalized for body weight. Although the compliance values ob-tamed in this way do not compare with values obtained by methods for measuring static compli-ance, Ashbaugh et al’ have found them valuable in

following

the

course

of ARDS.

Follow-up

information

was

obtained

from

clinic

visit

records

and

rehospitalization

records.

RESULTS

Fifteen

patients

who

fulfilled

the

criteria

for

ARDS were identified. The mean age was 5.7 years

(2)

TABLE. Patient Profiles

Case Age Sex Predisposing Illness Duration Max Peak Outcome

of Venti- PEEP Airway latory (cm Pressure

Support H20) (cm

H2O)

1 5 yr F Smoke inhalation 24 hr 15 . ..

CNS

death

2 6 yr F Postoperative blood aspirations;

respiratory arrest

26 days 22 80 Chronic interstitial infiltrates;

ob-structive lung disease

3 2.5 yr M Acute myelogenous leukemia;

en-terococcal pneumonia

4 hr 8 43 Respiratory death

4 3 yr M Near-drowning 6 days 8 40 Severe anoxic encephalopathy

5 5 yr F Near-drowning 2 hr 25 75 Respiratory death

6 14 yr F Systemic lupus erythematosus 32 days 20 50 CNS death

7 3.5 yr F Near-strangulation 4 days 10 45 CNS death

8 5 yr M Near-drowning 6 days 12 50 Normal

9 1 1 yr M Near-drowning 8 days 20 70 CNS death

10 15 mo M Near-strangulation 17 days 18 65 Generalized seizures; left

hemi-paresis;

mild developmental

de-lay

1 1 3.5 yr F Near-drowning 4 days 18 73 Respiratory death

12 1 1 yr F Near-drowning 7 days 17 . . . Normal

13 16 mo M Asphyxia secondary to balloon

as-piration

18 hr 12 48 CNS death

14 13.5 yr F Dermatomyositis; aspiration 18 days 20 52 Continued morbidity secondary to dermatomyositis

15 15 mo M Near-strangulation 6 days 13 50 CNS death

near-drowning (six patients) and accidental stran-gulation (three patients) (Table).

Ventilator therapy was delivered with a constant volume ventilator (Bennett MA-i, Kansas City,

MO). Mean duration of ventilator support was nine

days (range two hours to 32 days). Reasons for

initiating assisted ventilation were one or more of the following: (1) absence of respirations or ineffec-tive respirations following respiratory arrest (ii patients); (2) induction of hypocarbia (Pco2 <30

torr) as part of a regimen to control intracranial pressure (nine patients); (3) hypoxemia in 100% oxygen (Pao2 < 60 torr) (ten patients). All patients required 100% inspired oxygen at some point in their course. Mean peak airway pressure was 57 cm

H20

(range 40 to 80 cm H20) with no difference in mean peak pressures between those patients who lived or died. All patients received PEEP in an effort to increase arterial Po2. Five patients either had too short a hospital course or had insufficient records to assess accurately a PEEP response. The remaining ten patients demonstrated a mean in-crease of 8 ± 6 ton/cm H20 PEEP (i ± 1 SD). Average maximum PEEP was 16 cm H2O. In 6/10

patients, no PEEP response was noted until at least

10 cm H20 had been applied.

Central vascular monitoring was instituted in all children who survived more than 12 hours following admission. This was accomplished with either a

central venous catheter placed in the right atrium,

or with a flow-directed balloon-tipped catheter placed in the pulmonary artery. In addition, a

sys-temic arterial catheter was placed in all patients.

Mean

effective

dynamic

compliance

measured

at

the time of maximal ventilator support was 0.34 mJ/ cm H20/kg in children who survived and 0.30 ml/ cm H2O/kg in those who died. This difference was

not significant (Student’s unpaired t test). Values

obtained

for both

groups

were

less

than

50%

of the

expected

adult

normal

values

corrected

for

body

weight.

Nine of the 15 patients (60%) died; maximum survival was 32 days from the time of onset; mean

time

of death

was

six days following the insult. In

only three cases was death clearly associated with

refractory

hypoxemia.

The

six

other

children

died

from

irreversible

CNS

damage.

The

inspired

oxygen

required

by that

group

of six children

at the

time

of

death was <40%. All had demonstrated a decreased

need

for ventilatory

assistance

during

the

24 hours

prior

to

their

death

and

had

an

improved

chest

radiographic

appearance.

Air

leak,

the

most

common

acute

complication

of

ventilator therapy, occurred in ten patients. There

was

no

difference

in

the

level

of

peak

inspired

pressure

or level

of PEEP

in the

five

patients

not

developing

air leak compared to those who did.

Secondary

infection

was

suspected

in several

chil-dren

but

not

confirmed

by

premortem

positive

blood

cultures

in any.

One

postmortem

culture

of

lung

tissue

yielded

a growth

of

Enterococcus

(Ta-ble,

case

3).

Long-term

pulmonary

sequelae

were

minimal.

(3)

densi-. ‘:

,

. - ‘.. . .

“‘A

rwc.:.

ties on chest radiographs six months after discharge

and

another

had

persistent

interstitial

infiltrates

and obstructive lung disease with a 50% reduction

in the

one-second

forced

expiratory

volume

(FEy1),

when evaluated

nine

months

after

hospitalization.

Even

in

this

patient

an

unequivocal

relationship

between

ARDS

and

chronic

lung

disease

could

not

be established because an early childhood history

of recurrent aspiration pneumonia was present.

Four

of

six

children

survived

with

apparently

normal neurologic function. Two suffered major neurologic handicaps. One child with spastic

quad-riplegia,

generalized

seizures,

and

minimal

response

to aversive

stimuli

requires

institutional

care.

The

other

child

has

a generalized

seizure

disorder,

left

hemiparesis,

and

mild

delay

in development

as

mea-sured by the Gesell Development Schedule.

During

the

period

encompassed

by

this

study,

there

was

an

average

of

500 admissions to the

pediatric

intensive

care

unit

yearly.

The

incidence

of ARDS in this medical intensive care population is approximately 8.5 cases per i,000 admissions.

Two

illustrative

cases

are

presented.

Fig 1 . Chest radiograph of patient C.C. 12 hours after injury. Note bilateral infiltrates and thoracostomy tubes.

CASE REPORTS

Case 1

C.C. was a previously healthy 3-year-old white girl who sustained a strangulation injury when her poncho drawstring caught on a slide. She was found hanging from the slide five to ten minutes later by her father who immediately began mouth-to-mouth artificial ventilation. Following emergency transport to the local hospital, she was noted to be asystolic, a condition that was quickly reversed. Two hours later, following further resuscitation, she had some spontaneous respirations and equal and reactive pupillary reflexes. However, her corneal and gag reflexes were absent, and she demonstrated bilateral flac-cid paralysis.

Oliguria, hypotension, and cerebral edema were treated with fluid restriction, dopamine, and dexamethasone. A chest radiograph 12 hours after the injury showed diffuse alveolar infiltrates (Fig 1). Forty-eight hours following the injury, cardiopulmonary function had improved, and the patient required fractional inspiratory oxygen (FIO2) of 0.35 and PEEP of 8 cm H20 for adequate oxygenation. Nevertheless, neurologic functions deteriorated and by 72 hours after the injury, there was no sign of cerebral or brainstem activity. The patient died soon after. Her fmal chest radiograph is shown in Fig 2 and demonstrates improvement, correlating with her now minimal frac-tional inspiratory oxygen needs.

Case 2

L.P.

is a 6-year-old white girl admitted to Children’s Orthopedic Hospital for routine tonsillectomy and ade-noidectomy and placement of bilateral myringotomy tubes. Pertinent past history includes a

tracheoesopha-Fig 2. Chest radiograph of patient C.C. just prior to

death shows resolving pulmonary densities.

geal fistula repaired in the newborn period and recurrent

aspiration

pneumonia

secondary

to gastroesophageal

re-flux corrected by fundal plication at age 5 years.

(4)

‘,(.

: (Fig 3). Oxygenation improved with the application of

high leveLs of PEEP (maximum 22 cm H2O), but therapy was complicated by fluctuating fluid requirements,

exten-sive

subcutaneous

emphysema,

and

recurrent

bilateral

pneumothoraces. Gradual resolution of the air leak and pulmonary densities allowed weaning of supplemental oxygen and PEEP so that the ventilator was discontinued after 24 days. She was discharged one month later. On follow-up, she continues to have minimal interstitial in-filtrates on chest radiographs (Fig 4) with obstructive pulmonary disease as measured by reduced forced expir-atory flow.

DISCUSSION

Adult respiratory distress syndrome was initially described by Ashbaugh and associates’ in 1967. It

is now

commonly

recognized

in

adults with an es-timated yearly incidence of

i50,000

cases

and a

mortality of 25% to 59%4.5 In spite of the importance of this disease in adult medicine, the present report to our knowledge constitutes the first review of this

entity in children, and confirms a similarly high mortality.

The documentation of a comparable illness in the pediatric age group occurs in scattered case reports. Two articles dealing with heroin intoxication cite noncardiogenic pulmonary edema as the most com-mon complication. The first6 cites the development ofpulmonary edema in 28/49 patients, 50% of whom were between 14 and 17 years ofage, and the second

report7

establishes pulmonary edema in 71/149

pa-tients, 55% of whom were 2i years of age or less.

Pulmonary edema has also been described with

abuse of other depressant drugs including metha-done, barbituates, and

tranquiizers.’3’#{176}

Addition-ally, the findings of ARDS have been reported in

children with fresh and

salt

water immersion,”

cen-tral nervous system abnormalities,’2’3 fat embo-lism,’4”5 hanging,’6 hydrocarbon aspiration, trauma, and as a postoperative complication of cardiac

sur-gery.’7

The most common predisposing conditions in

adults are shock from any cause and thoracic and nonthoracic trauma. Pathophysiology of

this

entity is incompletely understood. The triggering insult initiates a series of events leading to injury of al-veolar septa, increased permeability of the pulmo-nary vascular endothelium, pulmonary microvas-cular platelet aggregation, and eventually intraal-veolar edema.4 The role of vasoactive substances

such as bradykinin and angiotensin I and II in this process remains undetermined, although the lung is central in mediating the normal metabolism of

these substances. Extensive damage to the

endo-thelium of the lung may alter local and circulating levels of vasoactive peptides, perhaps enhancing

the development of increased permeability and

in-, S-

‘‘

-.-‘,i-”

F

-:-

:

1I: 4

:‘

S “

Fig 3.

Chest

radiograph of patient L.P. Parenchymal

densities are uniform and diffuse. Note presence of pul-monary artery catheter.

Fig 4. Chest radiograph of patient L.P. six months after ifiness, showing minimal interstitial infiltrates.

terstitial and ultimately alveolar edema.’TM In the

present

series,

there

was a striking absence of

trauma victims. Neither were there any cases of

drug abuse or of overt bacterial pneumonia or

sep-sis. The syndrome appeared to develop most

corn-monly in association with a profound asphyxial

event.

There are no controlled evaluations of treatment

of children with ARDS. Extrapolations from the

adult literature give guidelines until such

evalua-tions take place.

Mechanical

ventilation with high

(5)

of

secretions from the airway by suctioning and physical therapy, and frequent changes of the

pa-tient’s

position

may

minimize

extensive

atelectasis

that appears to develop.4 Optimal fluid

manage-ment has not yet been established for ARDS. It is imperative not to administer excessive fluid to these patients and compound their pulmonary edema.

Application of continuous positive airway pres-sure is the single most important maneuver avail-able for improving oxygenation. This retrospective analysis of patient records showed a definite PEEP response in ten individuals. Recently Dantzker et

al,’9

using the multiple inert gas elimination tech-nique to study ventilation-perfusion abnormalities

in ARDS, showed that PEEP increases arterial Po2

by decreasing the perfusion of unventilated areas of

the lung. However, the response to PEEP is not

totally predictable and a minority of patients fail to improve or worsen with PEEP. Lamy and

co-work-ers2#{176}

showed

that

a rapid

and

marked

increase

in

Pa02 with application of PEEP was associated with improved survival. An important finding in the present study is the high levels of PEEP required

to improve arterial Po2. These values are two-fold

greater

than previously reported “optimal PEEP”

in

the treatment of hyaline membrane disease.2’ However, the application of high levels of PEEP cannot be advocated without a controlled study of associated morbidity.

Selection of optimal PEEP, the value at which maximal 02 transport occurs, may be facilitated by

measurements of cardiac output and

arterial-ye-nous Po2 differences, since PEEP is known to

de-press

cardiac

output,

even

while

raising

the

arterial

Po2. These measurements require invasive intra-vascular monitoring and are not without risks,22 but should prove useful in difficult cases. No

complica-tions attributable to arterial, central venous, or pulmonary artery catheters were noted in the pres-ent series of patients.

The three factors determining outcome are the degree of original injury, effectiveness of respiratory

support, and prevention of further pulmonary

in-jury.2 Morbidity is related to therapy and includes secondary infection, oxygen toxicity, compromised cardiac output, and air leak. Air leak was an espe-cially common finding in this series of patients, occurring in 66%.

The long-term outlook for normal pulmonary function in these children is not known. Residual pulmonary abnormalities (usually subclinical) have

been noted in approximately 40% of adults who

recover from ARDS. These abnormalities include

restrictive lung disease, impairment of pulmonary

gas

exchange,

accentuated

decline

in arterial

Po2

with exercise, and evidence of obstructive lung

dis-ease.2’26

In conclusion, the present study documents the

occurrence

of ARDS

in children.

The

results

sug-gest that although overall mortality is similar to that found in adults, death often occurs concomi-tantly with improving respiratory function. These findings highlight the need for a better understand-ing of the effects of arterial hypoxemia on a dam-aged brain, and a more broadly based systematic approach to therapy for these unfortunate children.

SUMMARY

Adult respiratory distress syndrome occurred in approximately 1% of the medical admissions to our pediatric intensive care unit during a consecutive 3#{189}-year period. It develops following some cata-strophic event or ifiness and is associated with a 60% mortality.

REFERENCES

1. Ashbaugh DG, Bigelow DW, Petty, TL, et al: Acute respi-ratory distress in adults. Lancet 2:319, 1967

2. Petty TL, Ashbaugh DG: The adult respiratory distress syndrome. Chest 60:233, 1971

3. Petty TL: The adult respiratory distress syndrome (confes-sions of a “lumper”), editorial. Am Rev Respir Dis 111:713, 1975

4. Hopewell PC, Murray JF: The adult respiratory distress

syndrome. Annu Rev Med 27:343, 1976

5. Amato JJ, Rheinlander HF, Cleveland LU: Post-traumatic adult respiratory distress syndrome. Orthop Clin North Am

9:693, 1978

6. Kaufman DM, Hegyi T, Duberstein JL: Heroin intoxication in adolescents. Pediatrics 50:746, 1972

7. Duberstein JL, Kaufman DM: A clinical study of an epi-demic of heroin intoxication and heroin-induced pulmonary edema. Am JMed 51:704, 1971

8. Frand UI, Shim CS, Williams MH, Jr: Methadone-induced

pulmonary edema. Ann Intern Med 76:975, 1972

9. Lindstr#{246}m FD, Flodmark 0, Gustafsson B: Respiratory dis-tress syndrome and thrombotic, non-bacterial endocarditis after amitriptyline overdose. Acta Med Scand 202:203, 1977 10. Schaff JT, Spivack ML, Rath GS, et al: Pulmonary edema

and adult respiratory distress syndrome following metha-done abuse. Am Rev Respir Dis 107:1047, 1973

11. Fandel I, Bancalari E: Near-drowning in children: Clinical aspects. Pediatrics 58: 573, 1976

12. Kosnik EJ, Paul SE, Rossel CW, et al: Central neurogenic pulmonary edema: With a review of its pathogenesis and treatment. Childs Brain 3: 37, 1977

13. Poe RH, Reisman JL, Rodenhouse TG: Pulmonary edema in cervical spinal cord injury. J Trauma 18:71, 1978

14. Murray DG, Racz GB: Fat-embolism syndrome (respiratory insufficiency syndrome). J Bone Joint Surg 56A:1338, 1974 15. Lamb AS: A severe case of fat embolism successfully treated

with positive end-expiratory pressure respiration. Resusci-tation 3:195, 1974

16. Herman SP: Recovery from hanging in an adolescent male.

Clin Pediatr 13:854, 1974

17. Kirby RR, Downs JB, Civetta JM, et al: High level positive end expiratory pressure (PEEP) in acute respiratory insuf-ficiency. Chest 67:156, 1975

18. Bedrossian CWM, Woo J, Miller WC, et al: Decreased angiotension-converting enzyme in the adult respiratory dis-tress syndrome. Am J Clin Pathol 70:244, 1978

19. Dantzker DR, Brook CJ, Dehart P, et al: Ventilation-perfu-sion distribution in the adult respiratory distress syndrome.

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20. Lamy, M, Fallat J, Koeniger E, et al: Pathologic features and mechanisms of hypoxemia in adult respiratory distress syn-drome. Am Rev Respir Dis 114:267, 1976

21. Bonta BW, Uauy R, Warshaw JB, et al: Determination of optimal continuous positive airway pressure for the treat-ment of IRDS by measurement of esophageal pressure. J

Pediatr 91:449, 1977

22. Dalen JE: Bedside hemodynamic monitoring, editorial. N

Engi JMed 301:1176, 1979

23. Rotman HH, Lavelle TF Jr, Dimcheff DG, et al: Long-term physiologic consequences of the adult respiratory distress

syndrome. Chest 72:190, 1977

24. Yohav J, Lieberman P, Molho M: Pulmonary function fol-lowing the adult respiratory distress syndrome. Chest 74:247, 1978

25. Lakshminarayan 5, Hudson LD: Pulmonary function follow-ing the adult respiratory distress syndrome. Chest 74:489, 1978

26. Simpson DL, Goodman M, Spector SL, et al: Long-term follow-up and bronchial reactivity testing in survivors of the adult respiratory distress syndrome. Am Rev Respir Dis 117: 449, 1978

EIGHTH CENTURY IRISH RULES REGARDING THE CARE

OF A SICK

PERSON

An early eighth century Irish manuscript contained the following sensible rules for the care of a sick person.

No

games

are

played

in the

house.

No tidings are announced.

No

children

are

chastised.

Neither

women

nor

men

exchange

blows.

There is no fighting.

The patient is not suddenly awakened.

No

conversation

is held

across

him

or across

his

pifiow.

No

dogs

are

let

fighting

in

his presence or in his neighborhood outside. No shout is raised.

No

pigs

grunt.

No

brawls

are

made.

No

cry

of victory

is raised.

Nor

shout

in playing

games.

No

shout

or scream

is raised.

REFERENCE

Noted by T.E.C., Jr, MD

(7)

1981;67;790

Pediatrics

Raymond K. Lyrene and William E. Truog

Conditions, Clinical Course, and Outcome

Adult Respiratory Distress Syndrome in a Pediatric Intensive Care Unit: Predisposing

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