Abstract in English:

ABSTRACT Objective To investigate the effects of lycopene supplementation on inflammation, lung histopathology and systemic DNA damage in an experimentally induced lung injury model, ventilated by conventional mechanical ventilation and high-frequency oscillatory ventilation, compared with a control group. Methods Fifty-five rabbits sampled by convenience were supplemented with 10mg/kg lycopene for 21 days prior to the experiment. Lung injury was induced by tracheal infusion of warm saline. The rabbits were randomly assigned to the control group and subjected to protective conventional mechanical ventilation (n = 5) without supplementation or the experimental group that was subjected to acute lung injury and provided conventional mechanical ventilation and high-frequency oscillatory ventilation with and without lycopene supplementation (n = 10 rabbits in each group). Lung oxidative stress and the inflammatory response were assessed based on the number of polymorphonuclear leukocytes in bronchoalveolar lavage fluid, DNA damage and pulmonary histological damage. Results A significant worsening of oxygenation and a decrease in static lung compliance was noted in all groups after pulmonary injury induction (partial pressure of oxygen before 451.86 ± 68.54 and after 71 ± 19.27, p < 0.05). After 4 hours, the high-frequency oscillatory ventilation groups with and without lycopene supplementation as well as the group receiving protective conventional mechanical ventilation with lycopene supplementation showed significant oxygenation improvement compared with the protective conventional mechanical ventilation group without supplementation (partial pressure of oxygen of the group with mechanical ventilation without lycopene of 102 ± 42, of the group that received conventional protective mechanical ventilation with lycopene supplementation of 362 ± 38, of the high-frequency group without lycopene supplementation of 420 ± 28 and of the high-frequency group with lycopene supplementation of 422 ± 25; p < 0.05). Compared with rabbits not receiving supplementation, those in the groups that received protective conventional mechanical ventilation with lycopene supplementation and high-frequency oscillatory ventilation with lycopene supplementation had significantly less inflammation as well as less histological injury (p < 0.05). Compared with rabbits subjected to protective conventional mechanical ventilation, significantly lower DNA damage was observed in rabbits supplemented with lycopene (p < 0.05). Conclusion Lycopene supplementation reduces inflammatory and histopathological lung injuries, regardless of the associated ventilatory mode. In addition, lycopene improved oxygenation and reduced DNA damage when protective conventional mechanical ventilation was used.

Abstract in English:

ABSTRACT Objective To define the incidence of ventriculostomy-associated infections and their impact on the mortality and functional outcomes of patients with aneurysmal subarachnoid hemorrhage. Methods We prospectively included all consecutive adult aneurysmal subarachnoid hemorrhage patients admitted to the neurological intensive care units of the Instituto Estadual do Cérebro Paulo Niemeyer (Rio de Janeiro, Brazil) and Hospital Cristo Redentor (Rio Grande do Sul, Brazil) who required external ventricular drains from July 2015 to December 2020. Daily clinical and laboratory variables were collected at admission and during the hospital stay. The presence of ventriculostomy-associated infections was evaluated daily, according to the Centers for Disease Control and Prevention and Infectious Diseases Society of America criteria. Hospital and 12-month outcomes were compared between patients with and without ventriculostomy-associated infections via both univariate and multivariate analyses. Results Out of the 676 patients screened, 271 received external ventricular drains (40%) and were included in the study. The mean age was 54 years (IQR 46–63), 198 were female (72%), 47% had poor grade status (World Federation of Neurological Surgeons scale 4 and 5), and 75% had modified Fisher 3 or 4. The mean time from admission to external ventricular drain placement was 8.8 days. Ventriculostomy-associated infections developed in 127 patients (47%), and the mean time from external ventricular drain to ventriculostomy-associated infection diagnosis was 4.4 days. Hospital and 12-month mortality rates did not differ between the ventriculostomy-associated infection group and the nonventriculostomy-associated infection group (36% versus 40% and 43% versus 49%, respectively). Poor functional outcomes, defined as modified Rankin scores of 4 to 6, showed no difference between groups at hospital discharge (ventriculostomy-associated infections 75% versus nonventriculostomy-associated infections 73%; p = NS) or at 12 months (ventriculostomy-associated infections 49% versus nonventriculostomy-associated infections 53%; p = NS). Conclusion Ventriculostomy-associated infections are common complications after aneurysmal subarachnoid hemorrhage. Although it was not associated with hospital mortality or functional outcomes in our cohort, improving diagnostic accuracy and preventive measures is essential for better understanding the long-term impact of one of the most severe infectious complications after aneurysmal subarachnoid hemorrhage.

Abstract in English:

ABSTRACT Objective Although the efficacy of high-flow nasal oxygen therapy in delaying or avoiding intubation in patients with hypoxemic respiratory failure has been studied, its potential for facilitating early weaning from invasive mechanical ventilation remains unexplored. Methods In this randomized controlled trial, 80 adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation for > 48 hours were enrolled and divided into two groups: conventional weaning and early weaning via high-flow nasal oxygen. In the conventional weaning group, the spontaneous breathing trial was performed after the PaO2/FiO2 ratio was ≥ 200, whereas in the high-flow nasal oxygen group, the spontaneous breathing trial was conducted earlier when the PaO2/FiO2 ratio was 150 - 200. Following each successful spontaneous breathing trial, patients were extubated and put on oxygen supplementation via a venturi mask or high-flow nasal oxygen on the basis of their group allocation. The primary objective was to compare extubation failure (reintubation within 48 hours). The secondary objectives were to compare total invasive mechanical ventilation, oxygen requirement and sedation requirement days, ventilator-associated pneumonia incidence, invasive mechanical ventilation-free days, intensive care unit length of stay, and intensive care unit all-cause mortality. Results Extubation failure was not significantly different between the high-flow nasal oxygen group and the conventional weaning group [12.5% versus 25%, respectively; odds ratio (95%CI) 0.5 (0.19 - 1.33)] (p = 0.25). Early weaning from invasive mechanical ventilation via high-flow nasal oxygen was associated with significantly increased invasive mechanical ventilation-free days and total oxygen requirement days (p = 0.02 and p = 0.01, respectively). No significant between-group differences were observed in total invasive mechanical ventilation days, ventilator-associated pneumonia incidence, intensive care unit length of stay, sedation duration, or all-cause mortality. Conclusion Among patients with acute hypoxemic respiratory failure, early extubation with high-flow nasal oxygen is a feasible and superior alternative to the conventional method of weaning, as it increases the number of invasive mechanical ventilation-free days.

Abstract in English:

ABSTRACT Objective This study aimed to explore the association between high outliers and intensive care unit admissions and to identify the factors contributing to high intensive care unit costs. Methods This retrospective cohort study used data from 17 Belgian hospitals from 2018 and 2019. The study focused on the 10 most frequently admitted diagnosis-related groups in the intensive care unit. The dataset included medical discharge summaries and cost per stay from the hospital perspective. Results A total of 39,279 hospital stays were analyzed, 11,124 of which were intensive care unit admissions; additionally, 2,500 of these stays were high outliers. The proportion of high outliers was significantly greater in the intensive care unit group, and admission to the intensive care unit was significantly associated with high outliers in the multivariate analyses. Factors associated with high intensive care unit outliers included the medical diagnosis-related group category, patients from nursing homes, intensive care unit stay duration exceeding 4 days, and specific technical procedures (measurement of intracranial pressure, continuous hemofiltration, and mechanical ventilation). Conclusion Admission to the intensive care unit increases the likelihood of being classified as an outlier, thus significantly impacting hospital costs. This study identified factors that can be used to predict intensive care unit outliers, which can enable adjustments to diagnosis-related group-based funding for intensive care units.

Abstract in English:

ABSTRACT Objective: To verify whether the rectus femoris muscle mass in mechanically ventilated patients assessed by ultrasonography at intensive care unit discharge is associated with functional status at hospital discharge. Methods: This cohort study was conducted at a tertiary hospital in Brazil between August 2019 and November 2020. We included patients over 18 years who were previously independent (Barthel index > 60) and underwent mechanical ventilation for at least 48 hours within 96 hours of admission. Ultrasonographic measurements of the rectus femoris cross-sectional area and right quadriceps thickness were performed upon enrollment, five days after enrollment, and at intensive care unit discharge. The primary outcome was assessing functional capacity via the Barthel index at hospital discharge. Results: Of the 78 patients included, 35 had assessable primary outcomes. Twenty (57.1%) patients were considered functionally dependent (Barthel index < 60). The Barthel index at hospital discharge was correlated with the cross-sectional area (r = 0.53; p = 0.001) and quadriceps thickness (r = 0.43; p = 0.01) at intensive care unit discharge. Multiple linear regression analysis revealed that the cross-sectional area at intensive care unit discharge was independently associated with the Barthel index. Conclusion: We found that muscle mass assessed by cross-sectional area ultrasonography at intensive care unit discharge was significantly correlated with functional capacity at hospital discharge.

Abstract in English:

ABSTRACT Objective: The goal of this study was to assess the Portuguese Intensive Care Referral Network, namely the mission and organization of the Portuguese National Health Service Intensive Care Medicine Services and patient flows between them. Methods: The study was based on the responses to a semi-structured questionnaire by the directors of the forty-one Intensive Care Medicine Services, characterizing four domains: a) number, type, and management of beds; b) human resources and their consumption; c) outreach, including activities in the resuscitation room, intra-hospital emergency team and follow-up clinics; and d) referral network. Results: The number of active Intensive Care Medicine Services beds in Portugal markedly increased in the last 12 years, but the beds/habitant ratio is still below the Organization for Economic Cooperation and Development average. The activation of all installed beds would likely allow for the reduction of the hospital care gap perceived by many of the Intensive Care Medicine Services directors. There is significant geographic heterogeneity in the beds/habitant ratio and in the performance of outreach activities. The number of intensivists is rapidly growing, but nursing staff should be augmented, especially rehabilitation nurses. The referral network is globally complied, but the secondary transport of critical patients needs improvement and an electronic information system, which can be constantly updated, is seen as a relevant decision aid. Conclusion: Although intensive care medicine has significantly strengthened in the last 12 years, both in number of beds and in role and mission, there is still relevant heterogeneity in the beds/habitant ratio and in the performance of outreach activities among different Intensive Care Medicine Services.

Abstract in English:

ABSTRACT Objective To identify predictive factors for failure in the installation of high-flow nasal cannulas in children diagnosed with acute viral bronchiolitis under 24 months of age admitted to the pediatric intensive care unit. Methods This work was a retrospective single-center cohort study conducted from March 2018 to July 2023 involving infants under 24 months of age who were diagnosed with acute viral bronchiolitis and who received high-flow nasal cannulas upon admission to the pediatric intensive care unit. Patients were categorized into two groups, the Success Group and Failure Group, on the basis of high-flow nasal cannula therapy efficacy. The primary outcome was treatment failure, which was defined as the transition to invasive or noninvasive ventilation. The analyzed variables included age, sex, weight, high-flow nasal cannula parameters, vital signs, risk factors, comorbidities, and imaging. Acute viral bronchiolitis severity was assessed using the Wood-Downes Scale, and functional status was assessed via the Functional Status Scale, both of which were administered by trained physiotherapists. Results In total, 162 infants with acute viral bronchiolitis used high-flow nasal cannulas, with 17.28% experiencing treatment failure. The significant differences between the Failure and Success Groups included age (p = 0.001), weight (p = 0.002), bronchiolitis severity (p = 0.004), initial high-flow nasal cannula flow (p = 0.001), and duration of use (p = 0.000). The cutoff values for initial flow (≤ 12L/min), weight (≤ 5kg), and Wood-Downes score (≥ 9 points) were determined from the ROC curves. Initial flow ≤ 12L/min was the most predictive for failure (AUC = 0.71; 95%CI: 0.61 - 0.84; p = 0.001). Multivariate analysis indicated that weight was a protective factor (RR = 0.87; 95%CI: 0.78 - 0.98), duration of use reduced the risk of failure (RR = 0.49; 95%CI: 0.38 - 0.64; p = 0.000), and Wood-Downes score was not significant (RR = 1.04; 95%CI: 0.95 - 1.14; p = 0.427). Weight explained 84.7% of the variation in initial flow. Conclusion Risk factors for high-flow nasal cannula therapy failure in bronchiolitis patients include younger age, consequently lower weight, and a lower initial flow rate.

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ABSTRACT Objective: To evaluate the ability of Brazilian pediatricians to recognize sepsis and septic shock in children. Methods: A cross-sectional multicenter survey was conducted among Brazilian pediatricians between May and June 2023, before the release of the new Phoenix sepsis criteria in 2024. An online electronic system was used for surveys to characterize the knowledge and skills of physicians in the diagnosis and treatment of sepsis in children. The questions related to the diagnosis and treatment of sepsis and septic shock in children were based on the International Pediatric Sepsis Consensus Conference, the American College of Critical Care Medicine Guidelines, and the Surviving Sepsis Campaign in Pediatrics. Descriptive statistical analyses were performed using R software. Results: Pediatricians were surveyed about the recognition, knowledge, and management of pediatric patients with sepsis and septic shock. The responses of 355 physicians from all regions of Brazil were analyzed, with the majority from the southeastern region of the country (53.3%). In clinical practice, the most utilized criteria for diagnosing sepsis included inappropriate tachycardia (92%), temperature alteration (88.2%), and the presence of a suspected or confirmed infectious focus (87.9%). For septic shock, capillary refill time alteration (87.1%), arterial hypotension (84.8%), and changes in the level of consciousness (82.2%) were the predominant indicators. A total of 55.6% pediatricians reported having the potential to obtain venous or intraosseous access within 5 minutes, and 59.3% could administer antibiotics within the first hour. Approximately one-quarter (27.5%) of the participants responded that it was possible to infuse 40 - 60mL/kg in 1 hour. The most commonly used solution for fluid resuscitation was isotonic saline (70.9%), followed by Ringer's lactate (45.0%). The infusion of a vasopressor was considered in patients who did not improve after receiving an infusion of 40 - 60mL/kg (75.8%). Conclusion: This is the first study to assess the knowledge of sepsis and septic shock among the Brazilian pediatric population. The results reveal a significant deficiency in the recognition of sepsis. This study demonstrated a gap between evidence and clinical practice. Adherence to international guidelines needs to be improved.

Abstract in English:

ABSTRACT Objective Agitation is a major problem in the intensive care unit. However, no treatment has clearly emerged as effective and safe. Using target trial emulation, we aimed to test the hypothesis that early intervention with dexmedetomidine would accelerate agitation resolution. Methods We read clinical notes in an electronic medical records system with natural language processing to identify patients with agitation. We obtained their demographics, trajectories, associations, and outcomes. We used g-formulas to study the possible effects of dexmedetomidine on agitation resolution and key outcomes. Results We screened 7525 patients. Overall, 2242 patients (29.8%) developed within-intensive care unit agitation, and 2052 (27.3%) were eligible for inclusion in the target trial emulation, with 314 treated with dexmedetomidine. Dexmedetomidine-treated patients had more severe illness and were more likely to have unplanned emergency admissions with medical diagnoses. However, they achieved higher rates of resolution of within-intensive care unit agitation (94% versus 72%; p < 0.001) and lower 30-day mortality (5% versus 9%; p = 0.033). Early initiation of dexmedetomidine accelerated the resolution of agitation (risk ratio [RR] 1.13 [95%CI 1.03 - 1.21]; risk difference [RD] 9.8% [95%CI 2.6% - 15.4%]); extubation by Day 30 (RR 1.03 [95%CI 1.02 - 1.04]; RD 3.1% [95%CI 2.2% - 4.2%]); and reduced the chance of having a tracheostomy by Day 30 (RR 0.67 [95%CI 0.34 - 0.99]; RD -3.5% [95%CI -7.0% - -0.0%]) Conclusion Through target trial emulation analysis, early dexmedetomidine was associated with an increased rate of resolution of agitation and extubation and decreased tracheostomy risk.

Abstract in English:

ABSTRACT Objective To perform a cross-cultural adaptation of the State Behavioral Scale to Brazilian Portuguese, assess its psychometric quality and use the scale to evaluate the level of sedation of patients on mechanical ventilation in the pediatric intensive care unit of a tertiary care hospital. Methods After receiving authorization by the main author, the State Behavioral Scale was adapted according to the following steps: translation of the original version into Portuguese; synthesis of the Portuguese versions; evaluation by a committee of judges; reverse translation by native speakers of the source language; synthesis of retroversions; pretest; and evaluation of psychometric quality. Results The adapted scale was administered to 20 patients by four evaluators, who performed daily evaluations in pairs simultaneously and independently. The intraclass correlation coefficient was 0.939 (p < 0.001) for the State Behavioral Scale and 0.976 (p < 0.001) for the COMFORT-B scale. The two scales were strongly correlated, with Spearman coefficients ranging from 0.884 to 0.908 (p < 0.001). In the study sample, most children (n = 43 observations; 48.9%) had scores of -1 (responsive to light touch or voice) or 0 (awake and able to calm down), which corresponded to light sedation. Conclusion The translated and adapted version of the State Behavioral Scale showed high interrater agreement and high correlation with the COMFORT-B scale. The application of the scale showed an adequate level of sedation in most patients.

Abstract in English:

ABSTRACT Background ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes. Objective To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial. Methods We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes. Conclusion According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study’s reported results.

Abstract in English:

ABSTRACT Background The perioperative management of patients undergoing cardiac surgery is highly complex and involves numerous factors. There is a strong association between cardiac surgery and perioperative complications. The Brazilian Surgical Identification Study (BraSIS 2) aims to assess the incidence of death and early postoperative complications, identify potential risk factors, and examine both the demographic characteristics of patients and the epidemiology of cardiovascular procedures. Methods and analysis BraSIS 2 is a multicenter observational study of patients who undergo cardiac surgery and who are admitted to the intensive care unit. The primary objective is to describe the risk factors and incidence of mortality or severe postoperative complications occurring within the first 3 postoperative days of cardiac surgery or until intensive care unit discharge (whichever event occurs first). Severe postoperative complications include acute myocardial infarction, acute respiratory distress syndrome, cardiorespiratory arrest with return of spontaneous circulation, Kidney Disease Improving Global Outcomes stage ≥ 2, a new surgical approach being conducted in an unscheduled event of urgency or emergency, renal replacement therapy, septic shock, severe bleeding, severe hemodynamic instability, stroke, unplanned reintubation, and unplanned use of a circulatory assistance device. The secondary outcomes include the evaluation of patient characteristics and descriptions of the performed surgeries and administered anesthesia. This study will also assess intraoperative and postoperative complications, as well as risk factors associated with postoperative complications and mortality. We expect to recruit 500 patients from at least 10 Brazilian intensive care units. Trial registration: NCT06154473; partial results.

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ABSTRACT Introduction: In patients with acute respiratory distress syndrome (ARDS), mortality risk is typically assessed using the arterial partial pressure of oxygen (PaO2) divided by the fraction of inspired oxygen (FiO2), known as the PaO2/FiO2 ratio. Recently, the SpO2/FiO2 ratio, which uses peripheral oxygen saturation (SpO2) instead of PaO2, has been suggested as a reasonable alternative when there is little access to arterial blood gas analyses. Additionally, equations that predict PaO2 from SpO2 values could offer another viable method for assessment. Aim: To evaluate the accuracy of methods for predicting PaO2 from SpO2 values and compare risk stratification based on measured versus predicted PaO2/FiO2 ratios using a large database that harmonizes the individual data of patients included in four observational studies. Methods and analysis: The individual data from four observational studies (‘Epidemiology of Respiratory Insufficiency in Critical Care study’ [ERICC], ‘Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure’ [LUNG SAFE], ‘PRactice of VENTilation in critically ill patients without ARDS’ [PRoVENT], and ‘PRactice of VENTilation in critically ill patients in Middle–income Countries’ [PRoVENT–iMiC]) were harmonized and pooled into a database named ‘PRoPERLy II’. The primary endpoint of this planned analysis will be the accuracy of currently available methods to predict PaO2 from SpO2 values. The secondary endpoint will be the accuracy of classification based on SpO2/FiO2 ratio and the predicted PaO2/FiO2 ratio. Dissemination: Our planned analysis addresses a clinically important research question by comparing different equations for predicting PaO2 from SpO2 values.

Abstract in English:

ABSTRACT Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.

Abstract in English:

ABSTRACT Technological advances and interprofessional teamwork have significantly improved survival rates of critically ill patients. However, this progress has also introduced new challenges, such as intensive care unit-acquired weakness, which can contribute to postintensive care syndrome. Both conditions are associated with increased morbidity and mortality, prolonged length of hospital stay, higher social and health care costs, and reduced quality of life for patients and their families. Timely physical therapy plays a crucial role in mitigating intensive care unit-acquired weakness and postintensive care syndrome. Key recommendations for the effective rehabilitation of patients in the intensive care unit include education and training, communication and collaboration, patient screening, planning of activities, distribution of functions focused on teamwork, patient cooperation, safety assessments, patient positioning, functional mobilization, and documentation of outcomes. This narrative review aims to update the current understanding of the influence of physical therapy and critical care teamwork on intensive care unit patients and to provide evidence-based recommendations for promoting early mobilization in the intensive care unit setting.

Abstract in English:

ABSTRACT Chronic dialysis patients account for a high proportion of intensive care unit admissions. The prevalent dialysis population is growing worldwide, accompanied by increasing medical complexity and comorbidities. Critical care physicians must be familiar with the unique clinical characteristics of this patient group. There is relatively little evidence specifically concerning the assessment and treatment of critically unwell individuals on long-term dialysis. This narrative review explores the approach to the management of chronic dialysis patients in the intensive care unit.

Abstract in English:

ABSTRACT Respect for autonomy and human vulnerability are bioethical principles that are frequently involved in decision-making dilemmas in the context of critical care. Multiple challenges are involved in the tasks of assessing and respecting the autonomy of critically ill patients with respect to the critical illness in question, patients' cognitive status and the context of intensive care units; furthermore, time constraints and emotional stress complicate decision-making for all stakeholders in this context. In addition, critically ill patients are inherently vulnerable to multiple sources of potential unintended harm. Therefore, clinicians working in intensive care units must develop the skills necessary to acknowledge, assess and mitigate those risks. In this manuscript, we review the literature on this topic. We also propose a practical approach that can help overcome some of those challenges; specifically, we advocate for the adoption of a relational approach to autonomy and shared decision-making, which could help overcome those challenges, thereby promoting more effective and ethical patient care.

Abstract in English:

ABSTRACT Apnea is a major complication of acute respiratory tract infection in young infants and may lead to the need for ventilatory support. Caffeine is methylxanthine, which is considered the mainstay of pharmacologic treatment for apnea of prematurity. On the basis of neonatal guidelines, caffeine has been used as a respiratory stimulant for the treatment of acute respiratory tract infection-related apnea, despite low evidence of its ability to improve clinical outcomes. Hyperlactatemia has been reported in adults with caffeine poisoning. Clarithromycin acts as an inhibitor of human cytochrome P450 and may impair drug metabolism. However, there are no published data concerning lactic acidosis associated with caffeine-clarithromycin coadministration. We report a case of hyperlactatemia in a young infant born prematurely who presented to the emergency department with acute respiratory tract infection-associated apnea and who required noninvasive ventilatory support. Because respiratory viruses were not detected in the nasopharyngeal aspirates and the chest radiography revealed interstitial opacities, clarithromycin (15mg/kg/day) was started via a nasoduodenal tube. In polysomnography, dysmaturity and immaturity of the central nervous system were evident. Hence, caffeine treatment was initiated at a loading dose of 10mg/kg followed by a maintenance dose of 5mg/kg/day. After treatment initiation, the child experienced ventilatory improvement and apnea control. However, a progressive increase in the serum lactate concentration and high anion gap metabolic acidosis were observed, despite hemodynamic stability. Following discontinuation of both drugs, the serum concentrations of lactate gradually returned to normal values. Thus, clarithromycin-caffeine coadministration may cause a sharp increase in lactate concentrations and should be avoided in young infants with acute respiratory tract infection-associated apnea.