Influence of pulmonary factors on pulse oximeter saturation in preterm infants.

AIM: To describe how the stability of oxygen saturation measured by pulse oximetry (SpO2%) varies within and between infants with bronchopulmonary dysplasia (BPD). METHODS: Clinically stable infants with BPD had SpO2 measured at different inspired oxygen concentrations (FIO2 expressed as %). A computer model of gas exchange, that is, ventilation/perfusion ratio (VA/Q) and shunt, plotted the curve of SpO2 versus FIO2 best fitting these data. The slope of this curve is the change in SpO2 per % change in FIO2, hence SpO2 stability, calculated at each SpO2 from 85% to 95%. RESULTS: Data from 16 infants with BPD previously described were analysed. The dominant gas exchange impairment was low VA/Q (median 0.35, IQR, 0.16-0.4, normal 0.86). Median shunt was 1% (IQR, 0-10.5; normal <2%). Slope varied markedly between infants, but above 95% SpO2 was always <1.5. In infants with least severe BPD (VA/Q ≈0.4, shunt ≤2%) median slope at 85% SpO2 was 5.1 (IQR, 3.7-5.5). With more severe BPD (VA/Q ≤0.3) slope was flatter throughout the SpO2 range. The highest FIO2 for 90% SpO2 was in infants with the lowest VA/Q values. CONCLUSIONS: In infants with BPD, there was large variation in the slope of the curve relating SpO2% to inspired oxygen fraction in the SpO2 range 85%-95%. Slopes were considerably steeper at lower than higher SpO2, especially in infants with least severe BPD, meaning that higher SpO2 target values are intrinsically much more stable. Steep slopes below 90% SpO2 may explain why some infants appear dependent on remarkably low oxygen flows.

A simplified method for deriving shunt and reduced VA/Q in infants.

BACKGROUND: Right to left shunt and regional hypoventilation (reduced ventilation/perfusion ratio (V(A)/Q)) have different effects on the curve relating inspired oxygen (P(I)O(2)) to oxygen saturation measured by pulse oximetry (SpO(2)) and can be derived non-invasively from measurements of SpO(2) and inspired oxygen pressure (P(I)O(2)) using complex models of gas exchange. We developed a simpler computerised "slide-rule" method of making these derivations. AIMS: To describe the slide-rule method and determine agreement between measurements derived with this and a more complex algorithm. METHODS: Series of P(I)O(2) versus SpO(2) data points obtained during 43 studies in 16 preterm infants with bronchopulmonary dysplasia were analysed. Percentage shunt and the degree of right shift (kPa) of the P(I)O(2) versus SpO(2) curve compared with the oxyhaemoglobin dissociation curve (a measure of V(A)/Q) were determined for each dataset with both methods, and the results were compared using the method of Bland and Altman. RESULTS: The computer slide-rule method produced results for all 43 datasets. The more complex model could derive results for 40/43 datasets. The mean differences (95% limits of agreement) between the two methods for measurements of shunt were -1.7% (-6.5 to +3.5%) and for measurements of right shift were 0.3 kPa (-2.9 to +3.6 kPa). CONCLUSION: The slide-rule method was reliable for deriving shunt and right shift (reduced V(A)/Q) of the P(I)O(2) versus SpO(2) curve when compared with the more complex algorithm. The new method should enable wider clinical application of these measurements of oxygen exchange.

Arterial oxygen tension (Pao2) values in infants <29 weeks of gestation at currently targeted saturations.

BACKGROUND: Oxygen saturation (Spo(2)) monitors are commonly used to determine the need for supplemental oxygen. We aimed to describe the range of arterial oxygen tensions (Pao(2)) observed in preterm infants at saturation levels targeted in current trials. METHODS: In a cohort of 98 consecutive infants born at <29 weeks' gestation, the Pao(2) from each arterial blood gas result during the first week of life (n = 2076) was matched to the Spo(2) at time of sampling. The mean (95% CI) Pao(2) was calculated for each saturation. RESULTS: The 95% CI of Pao(2) for the Spo(2) range 85-95% was 3.8 to 8.9 kPa. The mean (95% CI) Pao(2) at a saturation of 85% was 5.3 (3.8 to 6.8) kPa and at a saturation of 95% it was 7.2 (5.5 to 8.9) kPa. CONCLUSION: Saturations within the range 85-95% largely exclude hyperoxia in preterm infants <29 weeks' gestation but permit Pao(2) values far lower than those recommended in traditional guidelines.

Does the monitoring method influence stability of oxygenation in preterm infants? A randomised crossover study of saturation versus transcutaneous monitoring.

INTRODUCTION: Hyperoxia and variable oxygenation are associated with morbidity in preterm infants. The optimal range of oxygen tensions is not known. This study aimed to determine whether care based on transcutaneous oxygen tension (TcPO2) or saturation (SpO2) monitoring is associated with less time spent with high oxygen tension and less variability of oxygenation. METHODS: SpO2 and TcPO2 were measured simultaneously during two 3-h study periods allocated in random order. During one period supplemental oxygen was adjusted according to TcPO2 (target range 6.0-9.0 kPa) and during the other according to SpO2 (target range 86-94%). During each period, readings from the second monitor were not displayed. Both TcPO2 and SpO2 were downloaded every second. For each period the mean level and the variability (standard deviation) of SpO2 and TcPO2 and the percentage of time spent above and below target range were calculated and compared. RESULTS: 19 infants, 13 ventilated and 6 on continuous positive airway pressure, were studied at mean corrected gestational age of 27.2 weeks and mean postnatal age of 6.8 days. Their mean fraction of inspired oxygen at the start of the study was 0.34. Care based on SpO2 monitoring was associated with more time spent with high oxygen tension (median increase 2.62%, p = 0.01), more time with low oxygen tension (median increase 17.41%, p = 0.01), more variability in oxygen tension (median increase 0.28 kPa, p = 0.02) and more variability in oxygen saturation (median increase 0.82%, p = 0.01) than care based on TcPO2 monitoring. CONCLUSION: Within the target ranges studied SpO2 monitoring was associated with significantly more variable oxygenation than TcPO2 monitoring.

Non-invasive measurement of reduced ventilation:perfusion ratio and shunt in infants with bronchopulmonary dysplasia: a physiological definition of the disease.

BACKGROUND: An objective definition of bronchopulmonary dysplasia (BPD) is required to interpret trial outcomes and provide a baseline for prognostic studies. Current definitions do not quantify disease severity. The cardinal measures of impaired gas exchange are a reduced ventilation:perfusion ratio (V(A):Q) and increased right to left shunt. These can be determined non-invasively by plotting arterial oxygen saturation (Spo(2)) against inspired oxygen pressure (PIo(2)). AIMS: To describe the reduced V(A):Q and shunt in infants with BPD and evaluate these as graded measures of pulmonary dysfunction. METHODS: 21 preterm infants with BPD were studied. PIo(2) was changed stepwise to vary Spo(2) between 86% and 94%. Pairs of PIo(2) and Spo(2) data points for each infant were plotted and analysed to derive reduced V(A):Q ratio and shunt. RESULTS: In every infant, the Spo(2) versus PIo(2) curve was shifted to the right of the normal because of a reduced V(A):Q. The mean (SD) shift was 16.5 (4.7) kPa (normal 6 kPa). Varying degrees of shunt were also present, but these were less important in determining Spo(2) within the studied range. The degree of shift was strongly predictive of the PIo(2) required to achieve any Spo(2) within the range 86-94% (R(2)>0.9), permitting shift and V(A):Q to be determined from a single pair of PIo(2) and SpO(2) values in this range. CONCLUSIONS: The predominant gas exchange impairment in BPD is a reduced V(A):Q, described by the right shift of the Spo(2) versus PIo(2) relationship. This provides a simpler method for defining BPD, which can grade disease severity.

Cholinomimetics mimic efferent effects on semicircular canal afferent activity in the frog.

Acetylcholine (Ach) has received strong support as the neurotransmitter at vestibular efferent nerve endings. Ach, cholinomimetics and cholinergic antagonists were therefore applied to frog isolated whole labyrinths and isolated semicircular canals. Both spontaneous and evoked single unit and multiple unit activities were recorded from the decentralized posterior semicircular canal afferent nerve. In a manner analogous to efferent nerve stimulation, Ach produced both facilitatory and inhibitory changes in afferent firing rates. The facilitatory effect is likely mediated by muscarinic receptors (i.e. atropine antagonizes it at low concentrations). The facilitatory effect can also be elicited by muscarine and carbachol and it is likely produced presynaptically on the vestibular sensory cell. That is, the effects of Ach are not changed by removal of the efferent neurons but they are absent when afferent transmitter release is blocked. The inhibitory effect is not as well characterized as is the facilitatory effect but it can be blocked by strychnine. The results are consistent with the hypothesis that Ach is the transmitter responsible for both the facilitatory and the inhibitory effects of efferent vestibular nerve stimulation.

Amino-oxyacetic acid as a palliative in tinnitus.

Amino-oxyacetic acid, previously shown to cause a reversible loss of hearing sensitivity and a reduction in endocochlear potential, was tried as a palliative in human tinnitus. Because the drug seemed to have a cochlear site of action, patients were selected for the study if their audiograms were indicative of cochlear lesions and if there was a reduction in tinnitus following intravenous lidocaine (lidocaine positive). Ten such patients received either 50 or 75 mg of amino-oxyacetic acid four times a day orally for one week or placebo administered in a random, crossover, double-blind design. Of these ten, three reported subjective lessening of tinnitus. One of those three and two others not reporting subjective lessening of tinnitus showed a substantial improvement in speech discrimination scores while receiving amino-oxyacetic acid but not placebo. One additional patient who did not receive lidocaine also reported a subjective lessening of tinnitus. Four patients who were lidocaine negative showed neither subjective nor objective improvement in tinnitus after treatment with amino-oxyacetic acid.

Computer analysis of vestibular responses to putative neurotransmitters.

An inexpensive microcomputer (Commodore 64K) based system was developed for the analysis of neural spike trains. The trains were recorded from single ampullary units in response to mechanical stimulation of the isolated semicircular canal of the bullfrog (Rana catesbeiana). A BASIC program provided a number of options while machine language subroutines generated interstimulus interval (ISI) and peristimulus time (PST) histograms. Up to thirty 5-s spike trains could be combined for analysis (0.1 ms resolution ISI, 100 ms bin width PST). Histograms and summary statistics were saved on floppy disks. The cost of adding this computer system to an existing neurophysiology laboratory is less than US $600 (printed, tape, and disk versions of these programs are available). The system was used to measure vestibular responses to putative vestibular neurotransmitters such as carbachol (an acetylcholine mimic) (Rossi et al., 1980) and gamma-aminobutyric acid (GABA) (Flock and Lam, 1974).

Degraded discrimination between speech-like sounds by patients with multiple sclerosis and Friedreich's ataxia.

We previously found that some patients with multiple sclerosis are selectively 'deaf' to changes in the pitch of a tone, even when audiometric sensitivity to pure tones is unimpaired. This subtle form of deafness is not experienced by patients with noise-induced hearing loss of exclusively peripheral origin. It was suggested that this auditory defect may be one possible cause for difficulties in discriminating speech, on the grounds that frequency changes in the speech waveform are known to be important for intelligibility. This implication is not self-evident; our earlier studies tested hearing with a single pure tone that was either frequency-modulated or amplitude-modulated, while even a simple approximation to speech sounds involves not one, but three narrow bands of noise (formants) whose frequencies and intensities change from instant to instant. The present study has investigated the ability of subjects to discriminate between speech-like sounds. These consisted of three formant frequencies generated by computer. The only difference between the sounds was that the lowest-frequency formant rose or fell in pitch by different amounts. In order to ensure that subjects used frequency (pitch) cues rather than any associated loudness cues were mixed different loudness shifts with the frequency shifts. Nineteen control subjects, 25 patients with multiple sclerosis (MS) and 4 patients with Friedreich's ataxia (FA) were tested. Nine of the patients with MS and all 4 patients with FA gave results that fell outside the range of the control subjects. A possible pathophysiological basis for this observation is the finding that some neurons in the auditory pathway of animals respond preferentially to changes in tone frequency: homologues of these neurons might be functionally impaired in some patients with MS and FA.

The potentiation of ototoxicity when aminooxyacetic acid and kanamycin are co-administered.

Aminooxyacetic acid (AOAA) has been shown to confer protection against noise-induced cochlear trauma [3]. We, therefore, decided to study the possible protective effect of AOAA against kanamycin (KM) ototoxicity and found, instead, that AOAA potentiated the toxicity. To produce ototoxicity in guinea pigs, KM is usually given in 10-14 daily doses of 400 mg/kg s.c. However, when combined with a single dose of AOAA (8, 11, 15, or 25 mg/kg) a single 400 mg/kg dose of KM is sufficient to cause cochlear damage. Such animals show a negative Preyer's reflex between 1 to 3 days post injection. 21 days later hearing thresholds as detected electrocochleographically at 2, 4, 8, 12 and 16 kHz have changed drastically sometimes to the point of being undetectable. The damage seen histologically at this time is destruction of both inner and outer hair cells. A pharmacokinetic analysis of this potentiation revealed a slight prolongation of KM's sojourn in the inner ear. The possible mechanisms of this unexpected, marked potentiation are discussed but remain unknown.

Patients with multiple sclerosis experience hearing loss specifically for shifts of tone frequency.

After exposure to a prolonged tone of changing intensity but constant frequency, controls, patients with peripheral hearing loss, and patients with multiple sclerosis (MS) demonstrated a reduced sensitivity to shifts in intensity; sensitivity to frequency shifts was unaffected. After exposure to a prolonged tone of changing frequency but constant intensity, control and patients with peripheral hearing loss demonstrated reduced sensitivity to shifts in frequency; sensitivity to intensity shifts was unaffected. Some patients with MS showed no loss of sensitivity to shifts in frequency. Our findings suggest that some patients with MS have abnormal mechanisms for processing changes of frequency. If such processing of frequency change is important for understanding speech, then this observation of a specific central hearing defect may help to explain poor speech discrimination in some patients with MS who have normal audiograms.

Delayed auditory tone perception in multiple sclerosis.

Delays of auditory perception at three frequencies were measured in 30 multiple sclerosis patients using a psychophysical technique. Nineteen patients had abnormal delays at one or more tone frequencies, though 15 had normal audiograms at those frequencies. In addition, auditory acuity for left-right asynchrony was abnormally poor in 13 patients, 9 of whom had normal audiograms. Such delays of auditory perception within a restricted frequency band may provide a partial explanation for degraded speech comprehension in some multiple sclerosis patients.