Hemorrhages in Newborn Piglets Following Cardiopulmonary Resuscitation Retinal

James C. Fackler, MD; Ivor D. Berkowitz, MD; W. Richard Green, MD

Objective.\p=m-\Todetermine whether conventional cardiopulmonary resuscitation causes retinal hemorrhages in piglets. Design.\p=m-\Nonrandomizedobservations. Setting.\p=m-\Animalphysiology laboratory. Participants.\p=m-\Six3.5- to 4.5-kg piglets. Interventions.\p=m-\Fiftyminutes of conventional, closed chest cardiopulmonary resuscitation. \s=b\

Measurements/Main Results.\p=m-\Intrathoracic venous pressure (right atrium) and intracranial venous pressure (sagittal sinus) were directly measured. At 5 minutes of cardiopulmonary resuscitation, the mean (\m=+-\SEM)sagittal sinus pressure was 41 \m=+-\8mm Hg and the mean right atrial pressure was 58\m=+-\9mm Hg. The pressures were sustained throughout the 50 minutes of cardiopulmonary resuscitation. At autopsy, there was no gross or microscopic evidence of retinal hemorrhages. Conclusion.\p=m-\Theseresults support the conclusion that cardiopulmonary resuscitation does not cause retinal

hemorrhages.

(AJDC. 1992;146:1294-1296)

children, the clinical sign of retinal hemorrhages is In characteristic,1 pathognomonic,2 of the abused child authors that retinal hem¬ or even

syndrome. Many suggest orrhages are sufficient to diagnose child abuse, even with¬ out other more widely recognized signs of intentional trauma.3 Furthermore, the severity of retinal hemorrhage may correlate with the severity of neurologic damage. A quandary, however, in the effort to definitively attribute retinal hemorrhage to child abuse, is the frequent coinci¬ dence of alleged abuse and cardiopulmonary resuscitation (CPR). Cardiopulmonary resuscitation has been postu¬ lated to cause retinal hemorrhages. This study was designed to determine whether conven¬ tional CPR produces retinal hemorrhages in piglets. The pig is an appropriate model for ocular research because the retinal capillary networks of swine and humans are sim¬ ilar in size and distribution throughout the retinal layers.4 Accepted for publication July 14,

1992. From the Division of Pediatric Intensive Care, Department of Anesthesiology and Critical Care Medicine (Drs Fackler and Berkowitz), and the Departments of Ophthalmology and Pathology (Dr Green), The Johns Hopkins Medical Institutions, Baltimore, Md. Reprint requests to Multidisciplinary Intensive Care Unit, Children's Hospital, 300 Longwood Ave, Boston, MA 02115 (Dr Fackler).

Furthermore, pigs sustaining direct blunt trauma develop

retinal hemorrhages and other changes similar to humans.5

SUBJECTS, MATERIALS, AND METHODS experiments were performed on six 2-week-old piglets weighing from 3.5 to 4.5 kg. Anesthesia was induced with pentobarbital sodium (30 to 40 mg/kg intraperitoneally) and main¬ The

tained with intermittent doses of intravenous pentobarbital. Ventilation was performed via a tracheostomy with a Harvard animal ventilator with an inspired oxygen concentration of 30%. A saline-filled catheter, for pressure measurement, was placed in the right atrium via femoral vein cannulation. A catheter was placed in the axillary vein for fluid and drug administration. A burr hole was made in the skull over the midline, and a catheter was placed in the sagittal sinus. A bipolar electrode was placed in the right atrium from the femoral vein to induce ventricular fi¬ brillation. After surgery, pancuronium bromide (0.1 mg/kg) was administered. Before the induction of ventricular fibrillation and CPR, heparin sodium (1000 U) was administered. To better maintain perfusion pressures during CPR, each animal received a bolus and infusion of epinephrine hydrochloride. The vascular pressures were measured from the right atrium and sagittal sinus with Statham P23Db transducers (Statham In¬ struments Ine, Hato Rey, Puerto Rico) referenced to the level of the right atrium. Measurements of right atrial and sagittal sinus pressures were recorded before cardiac arrest and at 5,10, 20, 35, and 50 minutes during CPR (Table). Ventricular fibrillation was induced by passing 60 Hz AC resusci¬ through a right atrial pacing catheter. tation was commenced 15 seconds after induction of ventricular fibrillation. External chest compression was performed using a pneumatic chest compressor (Thumper, Michigan Instruments, Grand Rapids, Mich) equipped with a pediatrie chest pad. The force of the compressor was adjusted to produce 20% displace¬ ment of the anteroposterior chest diameter. The pneumatic chest compressor was cycled by a microprocessor that also initiates ventilation with a pressure-limited ventilator to peak pressures of 25 to 30 cm H20. The ventilation with 100% oxygen was interposed after every fifth chest compression. The compression rate was 100 per minute; the ventilation rate was 20 per minute. At the completion of each experiment, an autopsy was per¬ formed to confirm the catheter positions. The eyes were removed and placed in 4% formaldehyde solution for histologie process¬ ing. Twelve eyes were examined for gross and microscopic changes. Sections for histologie examination were taken in a plane through the pupil and optic nerve.

Cardiopulmonary

RESULTS The vascular pressure measurements generated during CPR are summarized in the Table. Mean right atrial près-

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Vascular Pressure Before and Pressure,

mm

Hg

Sagittal sinus Right atrial systolic Right atrial mean *Data are reported as mean ± SEM.

During Cardiopulmonary Resuscitation*

Baseline

5 min

10 min

20 min

35 min

50 min

5±2

41 ±8 94±12

44±6 110±15 73±9

44±4 114±18 71 ±12

44±4 108±18 74±12

42±6 105±19 74±12

9±3 4±2

58±9

sure rose with commencement of chest compressions from baseline and was sustained throughout 50 minutes of CPR at 58 to 74 mm Hg. Sagittal sinus pressure also rose rap¬ idly above baseline and was sustained at 41 to 44 mm Hg. Because of the persistent right atrial to sagittal sinus pres¬ sure gradient, transmission of intrathoracic venous pres¬ sures to intracranial veins was incomplete. Normal intraocular contents were seen in all eyes. Micro¬ scopically, all eyes showed normal cornea, iris, ciliary bod¬ ies, lenses, choroid, and optic nerves. There was no gross or microscopic evidence of retinal hemorrhages (Figure).

COMMENT Until recently, there has been no clinical evidence that CPR causes retinal hemorrhages. Kanter6 examined 44 children without previous trauma who underwent CPR, and found no retinal hemorrhages. One additional child in the series had retinal hemorrhages following CPR; the hemorrhages were likely caused by systemic arterial pres¬ sures in excess of three times normal for age. In a more re¬ cent report by Goetting and Sowa7 of 20 patients, two chil¬ dren developed retinal hemorrhages following CPR, without trauma as a confounding variable. One newborn received 75 minutes of CPR and could not be resuscitated. The authors added another patient with retinal hemor¬ rhages following CPR as an addendum to the series. Case reports of two other children are also suggestive,8-9 and a third case report is more convincing10 that CPR may indeed cause retinal hemorrhages. The mechanism of retinal hemorrhage has been debated for decades. Morris and Henkind11 reviewed, more than 20 years ago, the proposed hypotheses. They suggested there was no

single mechanism, but that, as commonly thought,

direct extension of subarachnoid blood was unnecessary. Other hypotheses at that time were (1) central retinal vein compression by extravasated blood and (2) sudden rises in intracranial pressure, causing stasis and rupture of the retinal vessels. In certain circumstances, retinal hemorrhages are caused by elevated intravascular pressure at eye level.12·13 Chest compression (classically seat-belt injuries), by transmitting intrathoracic to intraocular vascular pressure, is believed to cause retinal hemorrhages. Furthermore, Valsalva's maneuvers, by transmitting intra-abdominal to intraocular venous pressure, cause retinal hemorrhages by the same mechanism. Direct vascular damage from acceleration and deceleration forces have also been postulated as a cause of retinal hemorrhage. The pig is a good model for ocular research. That piglets can develop retinal hemorrhages is shown in a study of direct ocular trauma.5 The capillary network is of similar size and distribution in humans and swine. However, the pig has no central retinal artery, and major retinal vessels lie superficially.4

No gross

or

microscopic evidence of retinal hemorrhage after cardio¬

pulmonary resuscitation.

We found no evidence of retinal hemorrhage in a piglet model of CPR. Specifically, the high intrathoracic and sagittal sinus venous pressures in this model of CPR were not associated with retinal hemorrhages. Because cerebrospinal fluid pressure and intracranial vascular pressure rise similarly in this model of CPR, transmural pressures remain low, which may prevent vessel wall disruption. Whether a similar mechanism prevents retinal hemorrhage during CPR requires further study. It is known, however, that intraocular pressure and intracra¬ nial pressure vary similarly with changes in arterial partial pressures of carbon dioxide.14 These results support Kanter' s6 conclusion, based on a clinical study, that assignments of the cause of retinal hemorrhages be to child abuse rather than CPR when the two conditions are coincident.

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References

585-588. 8. Bacon CJ, Sayer GC, Howe JW. Extensive retinal haemorrhages in infancy: an innocent cause. BMJ. 1978;1:281. 9. Kirschner RH, Stein RJ. The mistaken diagnosis of child abuse: a form of medical abuse? AJDC. 1985;129:873-875. 10. Weedn VW, Mansour AM, Nichols MM. Retinal hemorrhage in an infant after cardiopulmonary resuscitation. Am J Forensic Med Pathol. 1990;

Caffey J. On the theory and practice of shaking infants: its potential residual effects of permanent brain damage and mental retardation. AJDC. 1972;124:161-169. 2. Eisenbrey AB. Retinal hemorrhage in the battered child. Childs Brain. 1.

1979;5:40-44.

3. Giangiacomo J, Barkett KJ. Ophthalmoscopic findings in occult child abuse. J Pediatr Ophthalmol Strabismus. 1985;22:234-237. 4. Rootman J. Vascular system of the optic nerve head and retina in the pig. Br J Ophthalmol. 1971;55:808-819. 5. Hart JCD, Blight R, Cooper R, Papakostopoulos D. Electrophysiological and pathological investigation of concussional injury: an experimental study. Trans Ophthalmol Soc U K. 1975;95:326-334. 6. Kanter RK. Retinal

11:79-82. 11. Morris DA, Henkind P. Relationship of intracranial, optic-nerve sheath and retinal hemorrhage. Am J Ophthalmol. 1967;64:853-859. 12. Lyle DJ, Stapp JP, Button RR. Ophthalmologic hydrostatic pressure syndrome. Am J Ophthalmol. 1957;44:652-657. 13. Byrnes VA. Elevated intravascular pressure as an etiologic mechanism in the production of eye injuries. Trans Am Ophthalmol Soc. 1959;57:473\x=req-\

hemorrhage after cardiopulmonary resuscitation or

538. 14. Smith RB, Aass AA, Nemoto EM. Intraocular and intracranial pressure during respiratory alkalosis and acidosis. Br J Anaesth. 1981;53:967-972.

child abuse. J Pediatr. 1986;108:430-432. 7. Goetting MG, Sowa B. Retinal hemorrhage after cardiopulmonary resuscitation in children: an etiologic reevaluation. Pediatrics. 1990;85:

In Other AMA

Journals

JAMA The Archives of Family Medicine: in the 1990s G. D.

Emphasizing Primary Care

Lundberg (JAMA. 1992;268:1596)

The Problem of Discrimination in Health Care D. C. Hadorn

Priority Setting

(JAMA. 1992;268:1454-1459)

An Introduction to the Philosophical Presuppositions of the Animal Liberation/Rights Movement R. P. Vance

(JAMA. 1992;268:1715-1719)

Infectious Diseases and Injuries in Child Opportunities for Healthier Children

Day Care:

S. B. Thacker; D. G. Addiss; R. A. Goodman; B. R. Holloway; H. C. Spencer (JAMA. 1992;268:1720-1726)

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