Moderate Hypoxemia Research Articles

Long-Term Oxygen Therapy in Patients With Chronic Obstructive Pulmonary Disease and Moderate Hypoxemia.

Long-Term Oxygen Therapy in Patients With Chronic Obstructive Pulmonary Disease and Moderate Hypoxemia.

Immobilization of Captive Wapiti Cervus canadensis with Azaperone and Xylazine

Abstract Xylazine, an α2-adrenoreceptor agonist, is commonly used in combination with other drugs for safe and effective immobilization of North American wapiti Cervus canadensis. Azaperone is a neuroleptic sedative that reduces the stress of immobilization and handling, but there are no reports of its efficacy when combined with xylazine for use in wapiti. Our objective was to test the efficacy of a combination of xylazine and azaperone to remotely immobilize captive wapiti for performing routine procedures. We administered drugs intramuscularly using a CO2-powered projector with commercially made darts. We successfully immobilized 11 of 12 wapiti with one remote injection containing estimated doses of 1.3 ± 0.05 mg/kg xylazine and 0.2 ± 0.03 mg/kg azaperone (mean ± SD), and immobilized animals were recumbent at 2–12 min after injection (mean: 6 min 40 s). We administered tolazoline as a reversal for xylazine at an estimated dose of 3.0 ± 0.6 mg/kg intramuscularly, and all wapiti were standing within 14 min of reversal administration. In a subset of three wapiti, a moderate hypoxemia occurred immediately after immobilization but resolved by 60 min, before xylazine reversal. The combination of xylazine and azaperone resulted in smooth and safe immobilization for performing routine processing in captive North American wapiti. Further studies are needed to determine whether this combination and dose of drugs would be sufficient for immobilization of free-ranging wapiti.

Hypoxemia in the ICU: prevalence, treatment, and outcome

BackgroundInformation is limited regarding the prevalence, management, and outcome of hypoxemia among intensive care unit (ICU) patients. We assessed the prevalence and severity of hypoxemia in ICU patients and analyzed the management and outcomes of hypoxemic patients.MethodsThis is a multinational, multicenter, 1-day point prevalence study in 117 ICUs during the spring of 2016. All patients hospitalized in an ICU on the day of the study could be enrolled. Hypoxemia was defined as a PaO2/FiO2 ratio ≤ 300 mmHg and classified as mild (PaO2/FiO2 between 300 and 201), moderate (PaO2/FiO2 between 200 and 101), and severe (PaO2/FiO2 ≤ 100 mmHg).ResultsOf 1604 patients included, 859 (54%, 95% CI 51–56%) were hypoxemic, 51% with mild (n = 440), 40% with moderate (n = 345), and 9% (n = 74) with severe hypoxemia. Among hypoxemic patients, 61% (n = 525) were treated with invasive ventilation, 10% (n = 84) with non-invasive ventilation, 5% (n = 45) with high-flow oxygen therapy, 22% (n = 191) with standard oxygen, and 1.6% (n = 14) did not receive oxygen. Protective ventilation was widely used in invasively ventilated patients. Twenty-one percent of hypoxemic patients (n = 178) met criteria for acute respiratory distress syndrome (ARDS) including 65 patients (37%) with mild, 82 (46%) with moderate, and 31 (17%) with severe ARDS. ICU mortality was 27% in hypoxemic patients and significantly differed according to severity: 21% in mild, 26% in moderate, and 50% in patients with severe hypoxemia, p < 0.001. Multivariate Cox regression identified moderate and severe hypoxemia as independent factors of ICU mortality compared to mild hypoxemia (adjusted hazard ratio 1.38 [1.00–1.90] and 2.65 [1.69–4.15], respectively).ConclusionsHypoxemia affected more than half of ICU patients in this 1-day point prevalence study, but only 21% of patients had ARDS criteria. Severity of hypoxemia was an independent risk factor of mortality among hypoxemic patients.Trial registration NCT 02722031

Impact of Gas Masks on Work of Breathing, Breathing Patterns, and Gas Exchange in Healthy Subjects.

The gas mask is used to protect military and non-military personnel exposed to respiratory hazards (chemical, biologic, radiologic, and nuclear agents). The objective was to evaluate the impact of the gas mask on indexes of respiratory effort and breathing patterns in a human model because no data exist. The design of the study was a crossover evaluation with four 10-min conditions in a randomized order: with and without wearing the gas mask when at rest and when exerting a standardized effort. During the studied conditions, 14 healthy subjects were evaluated for breathing patterns, indexes of respiratory effort (work of breathing, pressure-time product for esophageal pressure, and esophageal pressure swing) and capillary blood gases. Continuous SpO2 was recorded during the tested conditions. The indexes of respiratory effort significantly increased when subjects wore the gas mask under the tested conditions (at rest and during effort). The work of breathing was significantly augmented with the mask (at rest, 0.40 ± 0.32 J/cycle vs 0.25 ± 0.10 J/cycle; effort, 5.96 ± 3.32 J/cycle vs 4.43 ± 2.50 J/cycle; P < .001). The other indexes of effort (esophageal pressure-time product and esophageal swing were all significantly increased, from 30 to 60%, with a gas mask in comparison with at baseline without a gas mask). The impact on breathing patterns and PaCO2 was limited, without significant differences. Moderate hypoxemia was present during effort and was not increased by the gas mask. This study demonstrated a substantial increase in the indicies of respiratory effort both at rest and during exercise with a gas mask. Our measurements and findings may be referred in future research and development studies in this field. (ClinicalTrials.gov registration NCT02782936.).

MS # 20171964 / van den Heuvel - Goldilocks in the NICU—can oxygen be titrated “just right?”

Oxygen is the most commonly used “drug” for preterm infants, and recent large clinical trials highlight the need for careful titration within a narrow therapeutic window. In particular, lower achieved oxygen saturations are associated with increased mortality in extremely preterm infants, possibly due to more time spent in extreme hypoxemia. Automated systems that adjust the inspired oxygen based on the detected O2 saturation are a timely innovation that should improve the ease and precision of maintaining oxygenation within the desired range. Using an automated system, van den Heuvel et al found that a “narrow” target range for O2 saturation (88-92%) did not improve the time spent in the desired saturation range of 86-94%. However, the narrow range did reduce the time spent in moderate and severe hypoxemia (SpO2 <80%) and reduced the number of prolonged episodes of severe hypoxemia. Either approach was superior to manual adjustment and reduced time spent in hyperoxemia (Figure). The task of oxygen titration tends to fall on the shoulders of the busiest caregiver, the bedside nurse. Automated systems appear to go beyond relieving this burden to improve the precision and safety of oxygen therapy. Article page 36 ▶ Optimal Target Range of Closed-Loop Inspired Oxygen Support in Preterm Infants: A Randomized Cross-Over StudyThe Journal of PediatricsVol. 197PreviewTo investigate the effect of different pulse oximetry (SpO2) target range settings during automated fraction of inspired oxygen control (A-FiO2) on time spent within a clinically set SpO2 alarm range in oxygen-dependent infants on noninvasive respiratory support. Full-Text PDF

Supplemental oxygen in patients with stable chronic obstructive pulmonary disease: evidence from Nocturnal Oxygen Treatment Trial to Long-term Oxygen Treatment Trial.

Oxygen therapy was the first treatment shown to prolong life in patients with chronic obstructive pulmonary disease (COPD) and has been joined by lung volume reduction surgery in selected patients with emphysema, smoking cessation, and potentially noninvasive ventilation in chronic hypercapneic respiratory failure. Although there is consensus around the survival-enhancing effect of supplemental oxygen (SupplO2) for patients with chronic severe hypoxemia at rest, the impact of SupplO2 for COPD patients with moderate hypoxemia and exertional desaturation had been less clear. The recently published Long-term Oxygen Treatment Trial (LOTT) showed no benefit of SupplO2 for the composite outcome of survival and all-cause hospitalizations, or for component outcomes, severe COPD exacerbations, or quality of life in COPD patients with moderate resting hypoxemia or room air normoxemia with exercise desaturation. Results of the LOTT challenge the practice of prescribing SupplO2 for patients with COPD and moderate resting hypoxemia or isolated exertional desaturation. In the context that LOTT may not have recruited patients for whom SupplO2 conferred subjective benefit, there may be a role for short-term trials of SupplO2 with assessment of subjective benefit in such patients.

Assessment of Cardiac Vegetative Control during Acute Graduated Exogenous Normobaric Hypoxia in Rats.

The effects of exogenous normobaric hypoxic hypoxia on vegetative control of the heart and BP were examined in Wistar rats. The reference ranges of variation pulsometry parameters were determined in rats with normoxemia for 3 physiological variants of autonomic homeostasis: eutony, sympathicotony, and vagotony. Most rats (80%) demonstrated autonomic eutony. The study showed that saturation of arterial blood with oxygen is the most adequate assessment of severity of acute exogenous normobaric hypoxic hypoxia progressing within a closed hypoxic chamber, which standardizes this method and minimizes inaccuracies resulting from individual sensitivity to hypoxic stress. The changes in functional activity of systems that control the heart rhythm closely correlated with the drop in arterial blood oxygenation. While a small arterial hypoxemia activated the ergotropic elements of autonomic nervous system central subdivision accompanied by elevation of systolic BP, the moderate hypoxemia augmented the cholinergic influences and moderated the adrenergic ones under maintaining mobilization of the central autonomic nervous system-control loop and normotension. Severe hypoxemia was manifested by augmented influences from autonomic nervous system central subdivisions on the heart rate, disadaptation of the control systems, and systolic-diastolic arterial hypotension.

No benefit for oxygen in stable COPD with moderate hypoxemia

No benefit for oxygen in stable COPD with moderate hypoxemia

Which patients with moderate hypoxemia benefit from long-term oxygen therapy? Ways forward.

Long-term oxygen therapy (LTOT) improves prognosis in patients with COPD and chronic severe hypoxemia. The efficacy in moderate hypoxemia (tension of arterial oxygen; on air, 7.4−8.0 kPa) was questioned by a recent large trial. We reviewed the evidence to date (five randomized trials; 1,191 participants, all with COPD). Based on the current evidence, the survival time may be improved in patients with moderate hypoxemia with secondary polycythemia or right-sided heart failure, but not in the absence of these signs. Clinically, LTOT is not indicated in moderate hypoxemia except in the few patients with polycythemia or signs of right-sided heart failure, which may reflect more chronic and severe hypoxemia.

Waterpipe (narghile, hookah) tobacco smoking-induced acute eosinophilic pneumonia

Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, hypoxemic respiratory failure, and pulmonary eosinophilia. A temporal relationship has been described in a number of patients between the development of AEP and the recent onset of cigarette smoking. A 22-year-old male patient with no known chronic disease was admitted to the emergency service for 3 days with the complaints of cough, fever, dyspnea, and pleuritic chest pain. He was formerly a nonsmoker but was a waterpipe (narghile, hookah) tobacco smoker as a new habit once a night for the last 2 months. The erythrocyte sedimentation rate and C-reactive protein are elevated. Arterial blood gases revealed moderate hypoxemia. Computed tomography scans included bilateral, random, and patchy ground-glass opacities and also small bilateral pleural effusions. Echocardiograhic examination was normal. We had accepted the patient as an acute eosinophilic pneumonia due to rapid response to corticosteroid treatment, no microorganism in bronchoalveolar lavage (BAL) culture, and predominant eosinophilia was observed (70%–80%) in BAL.

Intraoperative factors associated with postoperative complications in body contouring surgery

BackgroundSeveral preoperative factors have been shown to influence outcome of body contouring surgeries. The effect of intraoperative features, including fluid volume administered, hemodynamic and respiratory parameters, and body temperature on postoperative complication, has not been reported to date. Materials and methodsAll subsequent patients undergoing body contouring surgery in the Tel Aviv Medical Center between 2007 and 2012 were enrolled. Demographic and intraoperative data were collected and analyzed for possible associations with postoperative complications, including formation of seroma, hematoma/bleeding, other surgical site complications (infection, adhesiolysis, or need for debridement), formation of a hypertrophic scar, any documented, infection or a composite outcome of any of the previously mentioned. ResultsData of 218 patients were assessed. Mean (standard deviation) age of patients was 41(14) y. Intraoperative administration of higher volumes of fluids was significantly associated with formation of seroma (P = 0.01), hematoma/bleeding (P = 0.03), hypertrophic scar (P = 0.01), surgical site complications (P = 0.01), and a composite outcome (P < 0.001). Development of hematoma/bleeding was associated with longer periods of low (<35.6°C) intraoperative core temperature (72% versus 50% of surgery duration in patients who did not develop this complication, P < 0.05). Surgical site complications were associated with longer periods of intraoperative oxygen desaturation (saturation ≤92%, 4.2% versus 0.9% of surgery duration in patients who did not develop surgical site complications, P < 0.01). ConclusionsIntraoperative moderate hypothermia, hypoxemia, and liberal fluid administration are associated with worse surgical outcome in patients undergoing body contouring surgery. Increased awareness of the potential adverse effects of these factors in body contouring surgery will enhance interventions aimed at avoiding and promptly treating such events.

Palliative oxygen for chronic breathlessness: what new evidence?

Supplemental oxygen improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia, but the effect of oxygen therapy in mild or moderate hypoxaemia to reduce symptomatic chronic breathlessness remains unclear. This review provides an overview of recent evidence about the role of oxygen therapy for the relief of chronic breathlessness in advanced illness. In COPD, a recent Cochrane review strengthens earlier findings regarding the positive effect of supplemental oxygen compared with air during exercise test in the training setting. The novel analysis of effect of oxygen therapy on quality of life (QoL) showed no clear effect. Short-burst oxygen therapy given before exercise had no effect and should not be used. Supplemental oxygen during exercise has been shown to reduce breathlessness in patients with COPD who have no or mild hypoxaemia, but it is not clear whether the reduction in breathlessness shown in the laboratory setting translates into a clinically important benefit. Further studies are needed to establish this.

219 - Mild to Moderate Hypoxemia among Stable Heart Failure Patients with Reduced Ejection Fraction: 24-hour Oxygen Monitoring

Introduction: Chronic heart failure (HF) patients with reduced ejection fraction experience dyspnea from fluid overload that may result in hypoxemia. Undetected hypoxemia may lead to fatigue, and reduced physical and cognitive performance reported by HF patients. Thus, understanding hypoxemia is critical to guide HF management, which may improve health outcomes. Aims: The primary aim was to compare 24-hour oxygen saturation (SpO2) between HF patients with optimal medical therapy and age-matched healthy participants. The secondary aim was to evaluate perceived physical function capacity and quality of life as correlates of SpO2 in the HF patients. The exploratory aim was to examine differences in 24-hour SpO2 between HF patients with NYHA classes I/II and III/IV. Methods: In this comparative study, 20 HF patients and 20 healthy adults completed 24-hour SpO2 monitoring using Nonin pulse oximetry. Inclusion criteria for HF patients were having systolic HF, LVEF <40%, and medically stable status confirmed by their HF cardiologist within past 2 weeks. Exclusion criteria included receiving oxygen therapy, having anemia, COPD, or sleep apnea. Duke Activity Status Index and Minnesota Living with Heart Failure were respectively used to measure perceived functional capacity and quality of life. Results: Mean ages were similar in HF patients and healthy adults (61 ± 16 vs. 55 ± 12 yrs, P = .256). Compared with age-matched healthy adults, HF patients had significantly higher frequency and longer duration of desaturation events, and lower average SpO2 (Fig. 1). Among the HF patients, 42% had SpO2 <95%. Oxygen saturation did not correlate with perceived functional capacity or quality of life in HF patients. Frequencies of NYHA classes were: I = 3, II=11, III=5, and IV = 1. Desaturation events did not significantly differ between NYHA classes I/II and III/IV. Post hoc analysis showed that the largest (312 ± 193) and the longest (197 ± 127 minutes) desaturation events were observed in NYHA class II. Conclusions: Despite receiving optimized medical care, HF patients still experienced mild to moderate hypoxemia. Hypoxemia may influence cognitive function by failing to supply necessary oxygen to the brain and thereby reduce the ability to perform HF self-care. Future studies need to be replicated in a larger sample with equal number of patients in each NYHA class.

Bedside Lung Ultrasonography in the Assessment of the Postoperative Atelectasis

Postoperative atelectasis may complicate the progress of patients after major abdominal surgery. Lung ultrasonography plays a key role in the diagnosis of lung consolidations (atelectasis, pneumonia, etc.) as it not only enables diagnosis at the patient's bedside, but also treatment response assessment in real time. We present the case of a patient who, at early stages of the postoperative period of major abdominal surgery, presented moderate hypoxemia secondary to the presence of bilateral alveolar consolidations which were diagnosed using bedside lung ultrasonography. These were resolved after treatment administration which was also assessed using bedside lung ultrasonography.

No benefit of long-term oxygen therapy in moderate hypoxaemia in COPD

No benefit of long-term oxygen therapy in moderate hypoxaemia in COPD

Persistent hypoxemia on ECMO

Extracorporeal membrane oxygenation (ECMO) is used to support patients with hypoxemia due to severe respiratory failure. Hypoxemia can persist during ECMO as a result of reduction in mechanical ventilatory support as part of a lung protective strategy, following which gas exchange provided by the native lungs is reduced or absent. If tissue oxygen delivery is maintained, mild to moderate hypoxemia will be well tolerated, but if tissue hypoxia develops, then the cause of hypoxemia must be addressed and corrected. Patterns of hypoxemia are dependent on the mode of ECMO support. During veno-venous support for respiratory failure, hypoxemia is global, with all tissues receiving hypoxemic blood. When femoral veno-arterial support is used in the presence of respiratory failure, then differential hypoxemia can result, with hypoxemia limited to the upper part of the body. The approach to hypoxemia is dependent on whether veno-venous (VV) or veno-arterial (VA) ECMO is used. Adequate oxygen saturation on VV ECMO requires adequate hemoglobin, a membrane lung operating below its rated flow, low recirculation, and extracorporeal circuit flow that captures most of the cardiac output. The approach to hypoxemia during VV ECMO includes addressing each of these. Identifying and limiting recirculation will improve effective extracorporeal flow. Anemia has two detrimental effects. First, it limits oxygen transfer through the membrane lung. Second, it increases oxygen extraction resulting in low mixed venous oxygen saturation that increases the effective venous admixture with circuit blood. Transfusion to near normal levels will help improve oxygen saturation. Increasing effective extracorporeal flow to capture at least 60% of the cardiac output is necessary.1 If the extracorporeal flow fraction is less than 60% due to an increased cardiac output, then reducing cardiac output through reducing exogenous catecholamines, use of beta blockade,2 or hypothermia3 will help improve the extracorporeal flow fraction. Hypothermia has the added benefit of reducing oxygen consumption and therefore improving mixed venous saturation. A final option is to leverage the native lungs, such as through prone positioning, as long as lung protective strategies can be maintained.4 Oxygen saturation on femoral VA ECMO is typically normal (>90%). The upper part of the body is provided with blood from the left ventricle that has been saturated by normally functioning lungs. The lower part of the body is provided with fully saturated blood from the extracorporeal circuit. The two circulations meet at some point in the aorta that depends on the relative magnitude of flow rate in these two circulations. If there is pulmonary dysfunction, then the blood ejected by the left ventricle will be hypoxemic, and tissues perfused proximal to the mixing point will be perfused with hypoxemic blood, while the lower body will have a normal saturation. Management of this differential hypoxemia is through improvement of pulmonary gas exchange if possible, increasing extracorporeal flow to decrease pulmonary blood flow, or conversion of VA ECMO to VVA (hybrid veno-arterial and veno-venous).

The Impact of Hypoxaemia on the Outcome in Liver Cirrhosis.

Prognostic factors for poor evolution are critical in the setting of limited access to liver transplantation for patients with cirrhosis. We aimed to investigate the impact of hypoxaemia on the outcome in cirrhosis and the evolution of arterial oxygen tension during long-term follow-up in these patients. Consecutive cirrhotic patients were prospectively enroled and followed-up in our tertiary referral center. Clinical features, biological tests, arterial blood gases, NT-proBNP levels, pulse oximetry measurements, 12-lead ECG, and transthoracic contrast echocardiography were documented on enrolment. The main outcomes were death and decompensation due to liver disease. 87 cirrhotic patients were included in the analysis and followed-up for a mean of 16 months. At enrolment, 27 (31%) patients were hypoxaemic, 19 had hepatopulmonary syndrome (HPS), but only 6 of those who were sampled at follow-up had persistent hypoxaemia. During the study period, 22 patients died of liver-related complications. Nine of them (41%) were hypoxaemic on enrolment but none had severe hypoxaemia. Hypoxaemia present at enrollment was not a risk factor for death (p=0.29) or decompensation of liver disease (p=0.7). A higher MELD score at baseline or increase during follow-up was a risk factor for death (p=0.02) and correlated with the presence of hypoxaemia. Normalization of the arterial oxygen levels was accompanied by a significant decrease in NT-proBNP (83 pg/ml vs 0 pg/mL, p=0.023). Mild and moderate hypoxaemia was frequent in our patients but was not associated with adverse outcome in cirrhosis. Repeated arterial blood gas sampling is advisable, especially in patients diagnosed with hepatopulmonary syndrome.

Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30–39 mmHg, 40–49 mmHg, 50–59 mmHg, and 60–69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60–80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood–brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

Lung protective mechanical ventilation strategies in cardiothoracic critical care: a retrospective study.

A body of evidence supports the use of low tidal volumes in ventilated patients without lung pathology to slow progress to acute respiratory distress syndrome (ARDS) due to ventilator associated lung injury. We undertook a retrospective chart review and tested the hypothesis that tidal volume is a predictor of mortality in cardiothoracic (medical and surgical) critical care patients receiving invasive mechanical ventilation. Independent predictors of mortality in our study included: type of surgery, albumin, H+, bilirubin, and fluid balance. In particular, it is important to note that cardiac, thoracic, and transplant surgical patients were associated with lower mortality. However, our study did not sample equally from The Berlin Definition of ARDS severity categories (mild, moderate, and severe hypoxemia). Although our study was not adequately powered to detect a difference in mortality between these groups, it will inform the development of a large prospective cohort study exploring the role of low tidal volume ventilation in cardiothoracic critically ill patients.

Transnasal administration of a combination of dexmedetomidine, midazolam and butorphanol produces deep sedation in New Zealand White rabbits

ObjectiveTo study the sedative and cardiorespiratory effects of transnasal (TN) administration of a combination of dexmedetomidine (DEX), midazolam (MID) and butorphanol (BUT) administered through a nasal catheter to rabbits undergoing diagnostic procedures. Study designDescriptive cross-sectional experimental study. AnimalsEight healthy New Zealand White rabbit does (12 ± 1 months old, 3.5 ± 0.3 kg). MethodsDEX (0.1 mg kg−1), MID (2 mg kg−1) and BUT (0.4 mg kg−1) were mixed (DMB) in a syringe and applied to the rabbits’ nasopharyngeal mucosa after the accurate catheterization of one nostril. The onset, duration and quality of effects including analgesia were scored using a numeric rating scale of sedation for rabbits. Continuous monitoring of vital parameters was performed via clinical and multiparametric recording. Physiological variables were explored using repeated measures anova for parametric data or Friedman's test for non-parametric data. Tukey's or Dunn's post hoc multiple comparisons test was used depending on normality. The statistical significance was set at p < 0.05. ResultsLoss of the righting reflex, deep sedation and profound analgesia ensued simultaneously at 1.4 ± 1.1 minutes after DMB administration. These effects lasted 45 minutes before subsiding into moderate sedation, which lasted for an additional 25 minutes. Residual central nervous system impairment persisted up to 100 minutes. Blood pressure dropped progressively over time by 50%, whereas respiratory frequency decreased by 70%, consistent with moderate hypoxemia and hypercarbia. Conclusion and clinical relevanceThe TN route is a reliable and effective means for administration of DEX, MID and BUT to rabbits. The overall profound sedative effects and analgesic proprieties of the DMB combination can be selectively reversed depending on the needs of the procedure. Oxygen supplementation and careful monitoring are mandatory even in healthy subjects. The DMB protocol should be cautiously used in rabbits with cardiovascular or respiratory deficiencies.