Effect of an Individualized Lung Protective Ventilation on Lung Strain and Stress in Children Undergoing Laparoscopy: An Observational Cohort Study.

BACKGROUND: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children. METHODS: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure. RESULTS: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum. CONCLUSIONS: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits.

The neural mechanism for Latent (fusion maldevelopment) nystagmus.

Latent nystagmus (LN) is the by-product of fusion maldevelopment in infancy. Because fusion maldevelopment--in the form of strabismus and amblyopia--is common, LN is a prevalent form of pathologic nystagmus encountered in clinical practice. It originates as an afferent visual pathway disorder. To unravel the mechanism for LN, we studied patients and nonhuman primates with maldeveloped fusion. These experiments have revealed that loss of binocular connections within striate cortex (area V1) in the first months of life is the necessary and sufficient cause of LN. The severity of LN increases systematically with longer durations of binocular decorrelation and greater losses of V1 connections. Decorrelation durations that exceed the equivalent of 2-3 months in human development result in an LN prevalence of 100%. No manipulation of brain stem motor pathways is required. The binocular maldevelopment originating in area V1 is passed on to downstream extrastriate regions of cerebral cortex that drive conjugate gaze, notably MSTd. Conjugate gaze is stable when MSTd neurons of the right and left cerebral hemispheres have balanced binocular activity. Fusion maldevelopment in infancy causes unbalanced monocular activity. If input from one eye dominates and the other is suppressed, MSTd in one hemisphere becomes more active. Acting through downstream projections to the ipsilateral nucleus of the optic tract, the eyes are driven conjugately to that side. The unbalanced MSTd drive is evident as the nasalward gaze-holding bias of LN when viewing with either eye.

Duration of binocular decorrelation predicts the severity of latent (fusion maldevelopment) nystagmus in strabismic macaque monkeys.

PURPOSE: Infantile esotropia is linked strongly to latent fixation nystagmus (LN) in human infants, but many features of this comorbidity are unknown. The purpose of this study was to determine how the duration of early-onset strabismus (or timeliness of repair) affects the prevalence of LN in a primate model. METHODS: Optical strabismus was created in infant macaques by fitting them with prism goggles on day 1 of life. The goggles were removed after 3 (n = 2), 12 (n = 1) or 24 weeks (n = 3), emulating surgical repair of strabismus in humans at 3, 12, and 24 months of age, respectively. Eye movements were recorded by using binocular search coils. RESULTS: Each animal in the 12- and 24-week groups exhibited LN and manifest LN, normal spatial vision (no amblyopia), and constant esotropia. The 3-week duration monkeys had stable fixation (no LN) and normal alignment indistinguishable from control animals. In affected monkeys, the longer the duration of binocular decorrelation, the greater the LN: mean slow-phase eye velocity (SPEV) in the 24-week animals was three times greater than that in the 12-week monkey (P = 0.03); mean LN intensity in the 24-week monkeys was three times greater than that in the 12-week monkey (P = 0.03). CONCLUSIONS: Binocular decorrelation in primates during an early period of fusion development causes permanent gaze instability when the duration exceeds the equivalent of 3 months in humans. These findings support the conclusion that early correction of infantile strabismus promotes normal development of cerebral gaze-holding pathways.

Decorrelation of cerebral visual inputs as the sufficient cause of infantile esotropia.

BACKGROUND AND PURPOSE: Human infants at greatest risk for esotropia are those who suffer cerebral insults that could decorrelate signals from the two eyes during an early critical period of binocular, visuomotor development. The authors reared normal infant monkeys under conditions of binocular decorrelation to determine if this alone was sufficient to cause esotropia, and associated behavioral as well as neuroanatomic deficits. METHODS: Binocular decorrelation was imposed using prism-goggles for durations of 3-24 weeks (control monkeys wore plano goggles), emulating unrepaired strabismus of durations 3 months to 2 years in human infants. Behavioral recordings were obtained, followed by neuroanatomic analysis of ocular dominance columns and binocular, horizontal connections in the striate visual cortex (area V1). RESULTS: Concomitant, constant esotropia developed in each monkey exposed to decorrelation for a duration of 6-24 weeks. The severity of ocular motor signs (esotropia angle; dissociated vertical deviation; latent nystagmus; pursuit / optokinetic tracking asymmetry; fusional vergence deficits), and the loss of V1 binocular connections increased as a function of decorrelation duration. Stereopsis was deficient and motion visually evoked potentials were asymmetric. Monkeys exposed to decorrelation for 3 weeks showed transient esotropia, but regained normal alignment, visuomotor behaviors, and binocular V1 connections. CONCLUSIONS: Binocular decorrelation is a sufficient cause of infantile esotropia when imposed during a critical period of visuomotor development. The systematic relationship between severity of visuomotor signs and severity of V1 connectivity deficits provides a neuroanatomic mechanism for these signs. Restoration of binocular fusion and V1 connections after short durations of decorrelation helps explain the benefits of early strabismus repair in humans.

Early versus delayed repair of infantile strabismus in macaque monkeys: II. Effects on motion visually evoked responses.

PURPOSE: Infantile strabismus in humans and the monkey is associated with maldevelopment of visual motion responsiveness, one manifestation of which is directionally asymmetric motion visual evoked potentials (motion VEPs). Early repair of strabismus in infant monkeys has been shown to restore normal development of motion responsiveness for pursuit and optokinetic eye movements (optokinetic nystagmus [OKN]). The purpose of this study was to determine how early versus delayed repair of strabismus influences the development or maldevelopment of motion VEPs. METHODS: Optical strabismus was created in infant macaques by fitting them with prism goggles on day 1 of life. The Early Repair group wore the goggles for a period of 3 weeks (the equivalent of 3 months before surgical repair in humans), whereas the Delayed Repair group wore the goggles for a period of 3 to 6 months (the equivalent of 12-24 months before surgical repair in humans). Several months after the removal of the goggles, motion VEPs to horizontally oscillating grating stimuli were recorded during monocular viewing. An asymmetry index (AI) was measured for each animal by extracting an asymmetric (F1) and symmetric (F2) frequency component from the motion VEP. The AIs of the infant monkeys with Early versus Delayed Repair were also compared with that of a group of adult monkeys, who had unrepaired, natural strabismus. RESULTS: When tested with a 1-cyc/deg, 6-Hz stimulus, both control and Early Repair monkeys exhibited symmetric motion VEPs (AI < 0.25). Mean AI was 0.15 +/- 0.09 in control and 0.16 +/- 0.13 in Early Repair monkeys. In contrast, both Delayed Repair and naturally strabismic monkeys had asymmetric motion VEP responses: AI = 0.57 +/- 0.22 in the Delayed Repair and 0.49 +/- 0.17 in the naturally strabismic monkeys (P < 0.01). Delayed Repair and naturally strabismic monkeys also had motion VEP asymmetries of equivalent magnitude when tested using stimuli at higher (3 cyc/deg/11 Hz) spatial-temporal frequencies. The concordance between motion VEP symmetry and normal fusional vergence was significant (P < 0.01). CONCLUSIONS: Early repair of optical strabismus in primates restores normal development of visual motion pathways in the cerebral cortex, measured as symmetric motion VEPs. Delayed repair causes permanent motion VEP maldevelopment. These results provide additional evidence that early strabismus repair is beneficial for brain development in infant primates.

Early versus delayed repair of infantile strabismus in macaque monkeys: I. ocular motor effects.

INTRODUCTION: The appropriate age for surgical correction of esotropic strabismus in human infants is controversial; some clinicians advocate surgery before age 6 months, and others recommend observation and surgery at older ages. Infantile (congenital) esotropia in humans and monkeys is known to be accompanied by a constellation of eye movement abnormalities caused by maldevelopment of cerebral visual motor pathways. The purpose of this study was to determine how early versus delayed correction of strabismus influences development and/or maldevelopment of these eye movement pathways. METHODS: Optical strabismus was created in infant macaques by fitting them with prism goggles on day 1 of life. The early correction group (2 experimental and 1 control) wore the goggles for a period of 3 weeks (the equivalent of 3 months before surgical repair in humans). The delayed correction group (3 experimental and 1 control) wore the goggles for a period of 3 or 6 months (the equivalent of 12 or 24 months before surgical repair in humans). Several months after the goggles were removed, the monkeys were trained to perform visual fixation, smooth pursuit, and optokinetic nystagmus (OKN) tasks for a juice reward. Eye movements were recorded using binocular search coils. The performance of the early versus delayed infant monkey groups was also compared with that of a group of adult monkeys who had unrepaired, naturally occurring infantile esotropia. RESULTS: Early correction monkeys developed normal eye movements and exhibited ocular motor behaviors that were indistinguishable from normal control animals. They regained normal binocular eye alignment and showed stable fixation (no latent nystagmus). Monocular horizontal smooth pursuit and large field OKN were symmetric. In contrast, delayed correction monkeys showed persistent esotropia, latent fixation nystagmus, dissociated vertical deviation, and pursuit/OKN asymmetry. Animals who had the longest delay in correction of the optical strabismus exhibited eye movement abnormalities as severe as those of adult animals with uncorrected, natural esotropia. CONCLUSIONS: Early correction of strabismus in primates prevents maldevelopment of eye movements driven by cerebral motor pathways. Our results provide additional evidence that early strabismus correction may be beneficial for brain development in human infants.

Ocular measurements throughout the adult life span of rhesus monkeys.

PURPOSE: To examine the relationship of ocular components to refraction throughout the adult life span of the rhesus monkey (Macaca mulatta). METHODS: Cycloplegic retinoscopy, A-scan ultrasonography, slit lamp examination, indirect ophthalmoscopy, and keratometry were performed in a cross-sectional study of 111 monkeys, aged 5 to 31 years. Lens thickness and anterior and vitreous chamber depths were measured from the echograms. The intercorrelations of these variables were analyzed, as well as their association with age and sex. RESULTS: In monkeys aged 5 to 15 years, the mean refractive value of +1.5 D with an SD of 1.7 D was maintained near the previously established developmental asymptote of +2 D. In monkeys older than 15 years, there was greater interindividual variation (SD = 4.5 D), including extreme myopia and hyperopia. The cornea became steeper with age. The axial length of the eyes increased up to 12 years of age and began to shorten after 20 years. Changes also occurred in the other individual components that constitute eye length. These age-related changes were decreased vitreous chamber depth, decreased anterior chamber depth, and increased lens thickness. In general, males had longer eyes than females. The eyes of old monkeys were more likely to exhibit cataract and drusen, but age-related changes in focal atrophy of the retinal pigment epithelium did not achieve statistical significance. CONCLUSIONS: The components of the monkey eye change with age in a pattern similar to that reported in humans. Age-related changes in individual ocular components that could be detrimental to refraction appear to be compensated for by changes in other components.