The effect of doxapram on survival and APGAR score in newborn puppies delivered by elective caesarean: A randomized controlled trial.

Doxapram is marketed as a respiratory stimulant and is used by some veterinarians to help with neonatal apnoea, especially in puppies delivered by caesarean. There is a lack of consensus as to whether the drug is effective and data on its safety are limited. Doxapram was compared to placebo (saline) in newborn puppies in a randomized, double-blinded clinical trial using two outcome measures: 7-day mortality rate and repeated APGAR score measurements. Higher APGAR scores have been positively correlated with survival and other health outcomes in newborns. Puppies were delivered by caesarean and a baseline APGAR score was measured. This was immediately followed by a randomly allocated intralingual injection of either doxapram or isotonic saline (of the same volume). Injection volumes were determined by the weight of the puppy and each injection was administered within a minute of birth. The mean dose of doxapram administered was 10.65 mg/kg. APGAR scores were measured again at 2, 5, 10 and 20 min. One hundred and seventy-one puppies from 45 elective caesareans were recruited into this study. Five out of 85 puppies died after receiving saline and 7 out of 86 died after receiving doxapram. Adjusting for the baseline APGAR score, the age of the mother and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the odds of 7-day survival for puppies that received doxapram compared to those that received saline (p = .634). Adjusting for the baseline APGAR score, the weight of the mother, the litter size, the mother's parity number, the weight of the puppy and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the probability of a puppy having an APGAR score of ten (the maximum APGAR score) between those that received doxapram compared to those that received saline (p = .631). Being a brachycephalic breed was not associated with an increased odds of 7-day mortality (p = .156) but the effect of the baseline APGAR score on the probability of having an APGAR score of ten was higher for brachycephalic than non-brachycephalic breeds (p = .01). There was insufficient evidence that intralingual doxapram provided an advantage (or disadvantage) compared to intralingual saline when used routinely in puppies delivered by elective caesarean and that were not apnoeic.

Preliminary evaluation of the effects of a 1:1 inspiratory-to-expiratory ratio in anesthetized and ventilated horses.

OBJECTIVE: To describe some cardiorespiratory effects of an inspiratory-to-expiratory (IE) ratio of 1:1 compared with 1:3 in ventilated horses in dorsal recumbency. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of eight anesthetized horses, with 444 (330-485) kg body weight [median (range)]. METHODS: Horses were ventilated in dorsal recumbency with a tidal volume of 15 mL kg-1 and a respiratory rate of 8 breaths minute-1, and IE ratios of 1:1 (IE1:1) and 1:3 (IE1:3) in random order, each for 25 minutes after applying a recruitment maneuver. Spirometry, arterial blood gases and dobutamine requirements were recorded in all horses during each treatment. Electrical impedance tomography (EIT) data were recorded in four horses and used to generate functional EIT variables including regional ventilation delay index (RVD), a measure of speed of lung inflation, and end-expiratory lung impedance (EELI), an indicator of functional residual capacity (FRC). Results were assessed with linear and generalized linear mixed models. RESULTS: Compared with treatment IE1:3, horses ventilated with treatment IE1:1 had higher mean airway pressures and respiratory system compliance (p < 0.014), while peak, end-inspiratory and driving airway pressures were lower (p < 0.001). No differences in arterial oxygenation or dobutamine requirements were observed. PaCO2 was lower in treatment IE1:1 (p = 0.039). Treatment IE1:1 resulted in lower RVD (p < 0.002) and higher EELI (p = 0.023) than treatment IE1:3. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that IE1:1 improved respiratory system mechanics and alveolar ventilation compared with IE1:3, whereas oxygenation and dobutamine requirements were unchanged, although differences were small. In the four horses where EIT was evaluated, IE1:1 led to a faster inflation rate of the lung, possibly the result of increased FRC. The clinical relevance of these findings needs to be further investigated.

Cardiovascular effects of two adenosine constant rate infusions in anaesthetized dogs.

OBJECTIVE: Adenosine induces vasodilatation. The aim of this study was to investigate cardiovascular effects of two adenosine constant rate infusion (CRI) doses in dogs. STUDY DESIGN: Experimental, longitudinal repeated measure design. ANIMALS: Ten healthy purpose-bred Beagle dogs. METHODS: Each dog was sedated with butorphanol. Anaesthesia was induced with propofol intravenously and maintained with sevoflurane (inspired oxygen fraction = 47-55%). Controlled mechanical ventilation was used to maintain normocapnia. Two doses of adenosine were administered as CRIs to each dog: 140 µg kg-1 minute-1 (A140) followed by 280 µg kg-1 minute-1 (A280). Pulse rate, invasive arterial pressure and stroke volume (by magnetic resonance phase contrast angiography) were measured at baseline, 3 minutes after starting adenosine and 3 and 10 minutes after discontinuing adenosine. Cardiac output, cardiac index and approximated systemic vascular resistances (approximate SVR) were calculated. Additionally, arterial blood gases, co-oximetry, electrolytes, glucose and lactate were measured and oxygen content and delivery calculated. One-way repeated measures analysis of variance (p < 0.05) was used for data analysis. RESULTS: A140 and A280 resulted in a significant decrease in arterial blood pressure [systolic (p = 0.008), mean (p = 0.003), and diastolic arterial pressure (p = 0.004)] and approximate SVR (p = 0.008) compared with baseline. No significant changes were detected for the other variables. All values returned to baseline within 3 minutes after adenosine discontinuation. CONCLUSIONS AND CLINICAL RELEVANCE: Adenosine CRI decreases arterial pressure by vasodilatation in healthy dogs. No additional effects were observed with the higher dose. The effects in compromised dogs remain to be investigated.

Monitoring changes in distribution of pulmonary ventilation by functional electrical impedance tomography in anaesthetized ponies.

OBJECTIVE: To assess changes in the distribution in pulmonary ventilation in anaesthetized ponies using electrical impedance tomography (EIT). STUDY DESIGN: Prospective experimental study. ANIMALS: A group of eight adult pony geldings. METHODS: General anaesthesia was induced and maintained using isoflurane in oxygen with volume-controlled ventilation [tidal volume (VT) (10 mL kg-1), respiratory rate (8-12 breaths minute-1)] to maintain end-tidal carbon dioxide between 35 and 40 mmHg (4.66-5.32 kPa). Regional distribution of ventilation was assessed with EIT (plane of fifth to sixth intercostal space) at 30, 60 and 90 minutes after intubation. The resulting functional images were divided into four regions of interest (ROI, A-D) to determine: 1) the ratio of VT distribution between dependent to nondependent lung (D/ND) and 2) changes in distribution within the lungs in the latero-lateral direction. The centre of ventilation (COV) was calculated. The dimension of the chest in the latero-lateral (W) and dorso-ventral (H) direction was measured at the height of the withers and the W/H ratio was calculated. The influence of time on the D/ND ratio, COV and ROI A-D were analysed with anova followed by post hoc Bonferroni tests. Pearson correlation coefficient and the coefficient of determination (r2) were calculated to evaluate the relationship between the W/H ratio and D/ND ratio, and COV. Statistical significance was set at p < 0.05. RESULTS: The median D/ND ratio (T30-T90) was 0.67 (0.40-1.01) and for COV 31.15% (11.20-45.20), confirming the expected uneven distribution of ventilation. The D/ND ratio had a moderate negative correlation with the W/H ratio (r = -0.68, r2 = 0.46, p < 0.001), while the COV did not correlate with the W/H ratio (r = -0.04). CONCLUSIONS AND CLINICAL RELEVANCE: Uneven ventilation in mechanically ventilated right laterally recumbent anaesthetized ponies occurs within 30 minutes and changed little over the following 60 minutes.

Impact of Trendelenburg (head down) and reverse Trendelenburg (head up) position on respiratory and cardiovascular function in anaesthetized horses.

OBJECTIVE: To describe the cardiorespiratory effects of a change in table position in anaesthetized horses. STUDY DESIGN: Prospective, crossover, randomized, experimental study. ANIMALS: Six adult horses (mean body weight 621 ± 59 kg, aged 13 ± 4 years). METHODS: The horses were anaesthetized twice in dorsal recumbency. They were either placed in the Trendelenburg position (head down; HD) followed by reverse Trendelenburg position (head up; HU) or in reverse order. Every position was maintained for 90 minutes. The order of positions was randomly assigned at initial anaesthesia. Extensive cardiorespiratory monitoring was performed. Statistical analysis consisted of a mixed model with horses as random effect and time, position, section of anaesthesia and interaction between those as fixed effects (p < 0.05). RESULTS: When HU was applied during the first section of anaesthesia, PaO2, (p = 0.012), oxygen saturation (SaO2, p < 0.01) and oxygen content (CaO2, p < 0.01) were significantly higher, while venous admixture (Q˙s/Q˙t, p < 0.01), mean arterial (p = 0.039), right atrial (p < 0.01) and mean pulmonary arterial pressure (p < 0.01) were lower than in HD. After changing from HU to HD, PaO2 and SaO2 remained higher and Q˙s/Q˙t lower compared to the inverse order. Independent of the order, in the HD position Q˙s/Q˙t (p = 0.019) increased while PaO2 (p < 0.01), SaO2 (p = 0.011), CaO2 (p < 0.01), venous PO2 (Pv¯O2; p = 0.019), venous saturation (p = 0.004) and venous oxygen content (p = 0.010) decreased over time. No significant differences were found for cardiac output, oxygen delivery, oxygen consumption and dobutamine requirement between the two positions. CONCLUSIONS AND CLINICAL RELEVANCE: Gas exchange is better preserved in HU compared to HD, especially if applied from the start of the anaesthesia.

Regional ventilation distribution and dead space in anaesthetized horses treated with and without continuous positive airway pressure: novel insights by electrical impedance tomography and volumetric capnography.

OBJECTIVE: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) on regional distribution of ventilation and dead space in anaesthetized horses. STUDY DESIGN: Randomized, experimental, crossover study. ANIMALS: A total of eight healthy adult horses. METHODS: Horses were anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous infusion in dorsal recumbency, and administered in random order either CPAP (8 cmH2O) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric capnography (VCap) measurements were performed every 30 minutes. Lung regions with little ventilation [dependent silent spaces (DSSs) and nondependent silent spaces (NSSs)], centre of ventilation (CoV) and dead space variables, as well as venous admixture were calculated. Statistical analysis was performed using multivariate analysis of variance and Pearson correlation. RESULTS: Data from six horses were statistically analysed. In CPAP, the CoV shifted to dependent parts of the lungs (p < 0.001) and DSSs were significantly smaller (p < 0.001), while no difference was seen in NSSs. Venous admixture was significantly correlated with DSS with the treatment time taken as covariate (p < 0.0001; r = 0.65). No differences were found for any VCap parameters. CONCLUSIONS AND CLINICAL RELEVANCE: In dorsally recumbent anaesthetized horses, CPAP of 8 cmH2O results in redistribution of ventilation towards the dependent lung regions, thereby improving ventilation-perfusion matching. This improvement was not associated with an increase in dead space indicative for a lack in distension of the airways or impairment of alveolar perfusion.

Agreement between invasive blood pressure measured centrally and peripherally in anaesthetized horses.

OBJECTIVE: To determine the agreement of invasive blood pressure measured in the facial, metatarsal and carotid arteries, and evaluate the effects of two haemodynamic conditions on agreement. STUDY DESIGN: Prospective randomized study. ANIMALS: A group of eight horses aged 7 (4-23) years with a body weight of 493 ± 33 kg. METHODS: Horses were anaesthetized and positioned in dorsal recumbency. Invasive blood pressure was measured simultaneously via catheters placed in the facial, metatarsal and carotid arteries. Cardiovascular function and agreement between arteries was assessed before and during administration of phenylephrine and sodium nitroprusside. These were administered until carotid mean pressure (MAPc) increased or decreased from baseline (65 ± 5) to >90 or <50 mmHg, respectively. Data recorded at each sample time included systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures for carotid (c), facial (f) and metatarsal (m) arteries as well as cardiac output (Q˙t) and systemic vascular resistance (SVR). Bland-Altman analysis was used to assess agreement between peripheral and central sites, and regression analysis to determine influence of Q˙t and SVR. RESULTS: The largest difference was observed in SAPc and SAPm with a bias and limits of agreement (LOA) of 2 (-15 to 19) mmHg. The bias (LOA) for MAPc and MAPf was 2 (-4 to 9) mmHg and for MAPc and MAPm was 5 (-4 to 14) mmHg. The best agreement for DAP was seen between DAPc and DAPf with bias (LOA) of 1 (-3 to 5) mmHg. Regression analysis indicated marginal influence on agreement by Q˙t on MAPc and MAPf. CONCLUSIONS AND CLINICAL RELEVANCE: MAP and DAP of the carotid artery were higher than those of the peripheral arteries, which may lead to overzealous treatment of hypotension, albeit maintaining central pressures. Q˙t and SVR did not largely influence the difference between sites.

Comparison of three continuous positive airway pressure (CPAP) interfaces in healthy Beagle dogs during medetomidine-propofol constant rate infusions.

OBJECTIVE: To compare the efficacy of three continuous positive airway pressure (CPAP) interfaces in dogs on gas exchange, lung volumes, amount of leak during CPAP and rebreathing in case of equipment failure or disconnection. STUDY DESIGN: Randomized, prospective, crossover, experimental trial. ANIMALS: Ten purpose-bred Beagle dogs. METHODS: Dogs were in dorsal recumbency during medetomidine-propofol constant rate infusions, breathing room air. Three interfaces were tested in each dog in a consecutive random order: custom-made mask (M), conical face mask (FM) and helmet (H). End-expiratory lung impedance (EELI) measured by electrical impedance tomography was assessed with no interface (baseline), with the interface only (No-CPAP for 3 minutes) and at 15 minutes of 7 cmH2O CPAP (CPAP-delivery). PaO2 was assessed at No-CPAP and CPAP-delivery, partial pressure of inspired carbon dioxide (PICO2; rebreathing assessment) at No-CPAP and the interface leak (ΔPleak) at CPAP-delivery. Mixed-effects linear regression models were used for statistical analysis (p<0.05). RESULTS: During CPAP-delivery, all interfaces increased EELI by 7% (p<0.001). Higher ΔPleak was observed with M and H (9 cmH2O) in comparison with FM (1 cmH2O) (p<0.001). At No-CPAP, less rebreathing occurred with M (0.5 kPa, 4 mmHg) than with FM (1.8 kPa, 14 mmHg) and with H (1.4 kPa, 11 mmHg), but also lower PaO2 was measured with M (9.3 kPa, 70 mmHg) than with H (11.9 kPa, 90 mmHg) and FM (10.8 kPa, 81 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: All three interfaces can be used to provide adequate CPAP in dogs. The leak during CPAP-delivery and the risk of rebreathing and hypoxaemia, when CPAP is not maintained, can be significant. Therefore, animals should always be supervised during administration of CPAP with any of the three interfaces. The performance of the custom-made M was not superior to the other interfaces.

Evaluation of three tidal volumes (10, 12 and 15 mL kg-1) in dogs for controlled mechanical ventilation assessed by volumetric capnography: a randomized clinical trial.

OBJECTIVE: To evaluate three routinely used tidal volumes (VT; 10, 12 and 15 mL kg-1) for controlled mechanical ventilation (CMV) in lung-healthy anaesthetized dogs by assessing alveolar ventilation (VTalv) and dead space (DS). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 36 client-owned dogs. METHODS: Dogs were randomly allocated to a VT of 10 (G10), 12 (G12) or 15 (G15) mL kg-1. After induction CMV was started. End-tidal carbon dioxide tension was maintained at 4.7-5.3 kPa by changing the respiratory frequency (fR; 630. VTalv kg-1 (p=0.001) increased and VDBohr (p=0.002) decreased with greater VT. VTCO2,br (p=0.017) increased and VDaw/VT (p=0.006), VDBE (p=0.008) and fR (p=0.002) decreased between G10 and G15. PIP (p=0.013) was significantly higher in G15 compared with that in G10 and G12. No changes were observed in MawP. CONCLUSIONS AND CLINICAL RELEVANCE: A VT of 15 mL kg-1 is most appropriate for CMV in lung-healthy dogs (as evaluated by respiratory mechanics and VCap) and does not impair cardiovascular variables.

Regional distribution of ventilation in horses in dorsal recumbency during spontaneous and mechanical ventilation assessed by electrical impedance tomography: a case series.

OBJECTIVE: To evaluate the regional distribution of ventilation in horses during spontaneous breathing and controlled mechanical ventilation (CMV) using electrical impedance tomography (EIT). STUDY DESIGN: Prospective, experimental case series. ANIMALS: Four anaesthetized experimental horses. METHODS: Horses were anaesthetized with isoflurane in an oxygen-air mixture and medetomidine continuous rate infusion, placed in dorsal recumbency with an EIT belt around the thorax, and allowed to breathe spontaneously until PaCO2 reached 13.3 kPa (100 mmHg), when volume CMV was started. For each horse, the EIT signal was recorded for at least 2 minutes immediately before (T1), and at 30 (n = 3) or 60 (n = 1) minutes after the start of CMV (T2). The centre of ventilation (CoV), dependent silent spaces (DSS) (likely to represent atelectatic lung areas), non-dependent silent spaces (NSS) (likely to represent lung areas with low ventilation) and total ventilated area (TVA) were evaluated. Cardiac output (CO) was measured and venous admixture and oxygen delivery (DO2) were calculated at T1 and T2. Data are presented as median and range. RESULTS: After the initiation of CMV, the CoV moved ventrally towards the non-dependent lung by 10% [from 57.4% (49.6-60.2%) to 48.3% (41.9-54.4%)]. DSS increased [from 4.1% (0.2-13.9%) to 18.7% (7.5-27.5%)], while NSS [21.7% (9.4-29.2%) to 9.9% (1.0-20.7%)] and TVA [920 (699-1051) to 837 (662-961) pixels] decreased. CO, venous admixture and DO2 also decreased. CONCLUSIONS AND CLINICAL RELEVANCE: In spontaneously breathing anaesthetized horses in dorsal recumbency, ventilation was essentially centred within the dependent dorsal lung regions and moved towards non-dependent ventral regions as soon as CMV was started. This shows a major lack of ventilation in the dependent lung, which may be indicative of atelectasis.