Permissive hypercapnia as a ventilatory strategy in burned children: effect on barotrauma, pneumonia, and mortality.

Sir, We read the article by Garg SK “Permissive hypercapnia: Is there any upper limit?”[1] with great interest. The author has rightly focused on a current protective lung ventilation strategy. Though there are several reports of extreme levels of hypercapnia tolerated by patients no safe upper limit has been described. We would like to add following facts. Permissive hypercapnia allows for low-tidal volume ventilation and hence minimizes ventilator associated lung injury. It also reduces inflammatory response in lungs by attenuating free radical formation, nuclear factor kappa-β activation and increased tumor necrosis factor-β, interleukin-1, 6, 8 production. On the contrary, it impairs plasma membrane wound healing in injured lungs in a pH dependent fashion[2] and also prevents alveolar fluid resorption by inhibiting Na-K ATPase of alveolar epithelial cells. Sustained hypercapnia in cases of pulmonary infection increases bacterial load and may further aggravate lung injury. Hence in conditions of sepsis associated lung injury permissive hypercarbia would be beneficial. Elevated CO2 level also induces mitochondrial dysfunction and impairs alveolar epithelial cell proliferation. Hypercapnic acidosis increases ventilatory drive and if patient is not properly sedated and paralyzed, patient-ventilator dyssynchrony may occur and result in increased transpulmonary pressure. Previous animal studies have reported vasogenic cerebral edema in hypercapnic acidosis and in human beings cerebral edema have been reported in severe respiratory acidosis associated with asthma.[3] Hypercapnia has a beneficial effect on brain in an optimal range. Lowering CO2 causes cerebral vasoconstriction whereas increased CO2 results in cerebral edema. Hence, like any other drug “permissive hypercapnia” should be used judiciously and under strict hemodynamic monitoring. Hypotension in this patient may not be attributed to hypercapnic acidosis. Though hypercapnic acidosis has a negative inotropic effect it increases net cardiac output by sympatho-adrenal stimulation and reduction in systemic vascular resistance.[4] Usually hypercapnic metabolic acidosis doesn't require buffering as it has less effect on the cardiovascular system. In situations where hemodynamic compromise occurs buffering should ideally be done by tris-hydroxy-amino-methane (THAM/Tromethamine), as it does not release CO2 and more effective in the correction of pH. Weber et al. have also found that THAM attenuates the reversible myocardial depressant action of permissive hypercapnia in patients with acute respiratory distress syndrome.[5] Last but not the least, it is not clear from the case whether the author tried recruitment maneuvers or how did they achieve optimum positive end-expiratory pressure as a strategy for open lung ventilation and preventing atelectrauma. Moreover, managing elevated PaCO2 by increasing tidal volume is now known to be unacceptable; however, management by increasing the respiratory rate, although common is of uncertain impact. For example, increasing respiratory rate frequency from 17 to 35/min adds over 25,000 additional opening and closing cycles per day to an already injured lung, and laboratory data suggest that this approach is associated with additional lung injury.[6]

Postoperative pulmonary complications draws anesthetists′ attention as it can be associated with prolonged postoperative hospital stays, increased hospitalization expense, retardeding postoperative recovery and increased hospital mortality. In recent years, lung protective ventilation strategy has been applied during operation under general anesthesia, and current protective lung ventilation strategies generally involve some degree of hypercapnia. Increasing evidences support that hypercapnia is well tolerated and hypercapnia can attenuate the inflammatory response during lung injury, which would assign it a specific role within lung protection strategies during mechanical ventilation. In this paper, we summarize the influence of permissive hypercapnia on the body and the research development in the application of permissive hypercapnia in general anesthesia. Key words: Pulmonary ventilation; Anesthesia, general; Permissive hypercapnia; Review

Modern ventilation strategies for patients with acute lung injury and acute respiratory distress syndrome frequently result in hypercapnic acidosis (HCA), which is regarded as an acceptable side effect ('permissive hypercapnia'). Multiple experimental studies have demonstrated advantageous effects of HCA in several lung injury models. To date, however, human trials studying the effect of carbon dioxide per se on outcome in patients with lung injury have not been performed. While significant concerns regarding HCA remain, in particular the possible unfavorable effects on bacterial killing and the inhibition of pulmonary epithelial wound repair, the potential for HCA in attenuating lung injury is promising. The underlying mechanisms by which HCA exerts its protective effects are complex, but dampening of the inflammatory response seems to play a pivotal role. After briefly summarizing the physiological effects of HCA, a critical analysis of the available evidence on the potential beneficial effects of therapeutic HCA from in vitro, ex vivo and in vivo lung injury models and from human studies will be reviewed. In addition, the potential concerns in the clinical setting will be outlined.

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system.Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome.Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit.

Traditional lung-protective ventilation strategies (LPVS) are currently used to reduce the incidence of postoperative pulmonary complications (PPCs), including low tidal volume (VT), positive end-expiratory pressure (PEEP), low inspiratory plateau pressure (Pplat), permissive hypercapnia, and recruitment maneuver (RM). However, a meta-analysis showed that high driving pressure was closely associated with the incidence of PPCs, but not with PEEP or VT, which led to the driving pressure-guided ventilation strategy. Some studies have proved that the driving pressure-guided ventilation strategy is superior to the traditional LPVS in reducing the incidence of PPCs. The purpose of this review is to present the current research progress and application of driving pressure-guided ventilation strategy.

Introduction: Advancements in extracorporeal membrane oxygenation (ECMO) have reshaped the landscape of critical care, enabling lung rest and support in severe respiratory failure. However, ventilator management during ECMO remains an area of evolving practice with no universally accepted standard. While traditional lung-protective strategies dominate, novel approaches aimed at further minimizing ventilator-induced lung injury (VILI) and enhancing lung recovery are gaining traction. This review highlights new and rising ventilation strategies in the management of ECMO-supported patients. Methods: A literature review was conducted using PubMed, Embase, and Cochrane databases for studies published between January 2012 and March 2024. Search terms included “ECMO,” “mechanical ventilation,” “ultraprotective ventilation,” “awake ECMO,” “spontaneous breathing,” and “adjunctive strategies.” Included studies were clinical trials, cohort studies, case series, and expert guidelines addressing novel ventilator approaches in adult patients receiving either veno-venous (VV) or veno-arterial (VA) ECMO. Results: Emerging ECMO ventilation strategies include ultraprotective (≤4 mL/kg) and near-apneic ventilation, as well as spontaneous breathing protocols. Early mobilization and awake ECMO allow lower sedation, preserved diaphragm function, and earlier weaning. Advanced modes like Neurally Adjusted Ventilatory Assist (NAVA) and Proportional Assist Ventilation (PAV) aim to synchronize effort while limiting lung stress. Adjuncts such as prone positioning, permissive hypercapnia, and variable ventilation may improve recruitment and oxygenation. These approaches may enhance recovery and reduce VILI, though high-quality data are limited. Conclusions: Ventilation management in ECMO is shifting beyond traditional lung-protective frameworks toward individualized, dynamic approaches that emphasize lung rest, patient interaction, and early recovery. Novel strategies such as ultraprotective ventilation, awake ECMO, and synchrony-promoting modes are redefining care paradigms. Further randomized trials are needed to establish the safety, efficacy, and long-term outcomes of these rising approaches.

Smoke inhalation-associated acute lung injury (SI-ALI) is a major cause of morbidity and mortality in victims of fire tragedies. To date, there are no evidence-based guidelines on ventilation strategies in acute respiratory distress syndrome (ARDS) after smoke inhalation. We reviewed the existing literature for clinical studies of salvage mechanical ventilation (MV) strategies in patients with SI-ALI, focusing on mortality and pneumonia as outcomes. A systematic search was designed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Risk of bias assessment was performed using the Newcastle-Ottawa Quality Assessment Scale (NOS; 0 to 9 stars), with a score ≥7 being the threshold for inclusion in the meta-analysis. A systematic search strategy was used to search 10 databases. Clinical studies were included in which patients: (1) experienced smoke inhalation, (2) treated with MV, and (3) described a concurrent or historical control group. A total of 226 potentially relevant studies were identified, of which 7 studies on high-frequency percussive ventilation (HFPV) met inclusion criteria. No studies met inclusion for meta-analysis (NOS ≥ 7). In studies comparing HFPV to conventional mechanical ventilation (CMV), mortality and pneumonia incidence improved in 3 studies and remained unchanged in 3 others. No change in ventilator days or ICU length of stay was observed; however, oxygenation and work of breathing improved with HFPV. Mechanical ventilation in patients with SI-ALI has not been well studied. High-frequency percussive ventilation may decrease in-hospital mortality and pneumonia incidence when compared to CMV. The absence of "good" quality evidence precluded meta-analysis. Based upon low-quality evidence, there was a very weak recommendation that HFPV use may be associated with lower mortality and pneumonia rates in patients with SI-ALI. Given SI-ALI's unique underlying pathophysiology, and its potential implications on therapy, randomized controlled studies are required to ensure that patients receive the safest and most effective care. The study was registered with PROSPERO International prospective register of systematic reviews (#47015).

IntroductionBurn injuries are life-threatening conditions consisting of elevated oxidative stress, severe inflammation, and an increased hypermetabolic and catabolic state. It is recommended to start enteral nutrition (EN) early in the burn injured patients. These patients undergo many operations, and with stopping of EN the intermittent caloric deficit multiplies. This leads to increased risk of negative outcomes. We sought to analyze the efficacy of continuing EN feedings during burn surgeries to maximize caloric intake while also evaluating for adverse outcomes such as pneumonia.MethodsA retrospective chart review of intraoperative feeding and pneumonia rates in pediatric and adult burn patients admitted during 2011-2017 to a regional burn center was conducted. Inclusion criteria included patients with secured airway via endotracheal tube or tracheostomy, mechanical ventilation for at least four days, and those who received EN during operations. The 2017 National Burn Repository (NBR) was used as the control population with mechanical ventilation ≥4 days and a yes/no pneumonia diagnosis. Our assumption was that these patients likely did not receive intraoperative EN as this is not standard protocol at this time.Results67 patients from our center and 779 NBR patients met inclusion criterion. EN were provided in 49-79% of total operations in the study group. The study group had a longer length of stay (LOS: 62 ± 34.4 vs 41 Days ± 31.7; p< 0.0001), Ventilator days (39 ± 28.9 vs 23 ± 43.9; p< 0.0001) and total body surface area burn percentage (TBSA: 36 ± 21 vs 31 ± 23 p-0.029).The relationship between pneumonia, inhalation injury, COPD, diabetes, and current smoking status was examined in the case population. The odds of a patient with inhalation injury developing pneumonia was 2.83 times greater than a patient without an inhalation injury. There was a higher pneumonia rate in the study group compared to control population (56.7% vs 18.9%; p< 0.0001). However based on a multinomial logistics regression analysis, there was no statistically significant association between intraoperative feeding and pneumonia in the study group (p-0.597).ConclusionsWe found a significant difference in the occurrence of pneumonia in our patient group compared to the NBR population, but our patients had higher LOS, ventilator days and TBSA burns. This suggest that our study group may have had higher acuity increasing risk of pneumonia. Our pneumonia rates do correspond with the rates reported from other comparable populations of burn patients. Despite this we did not find and association suggesting intraoperative feedings as the cause.

Undoubtedly, evidence-based medicine has contributed substantially to improve the quality of medicine in general, and in neonatology in particular [2]. However, quite often clinical studies performed in neonatology fail to provide clear evidence that a particular intervention is beneficial for the premature infant [1]. Often, only a trend can be seen, or statistically significant changes can only be seen for shortterm outcome parameters (e.g. ventilated days) [3], but not for long-term outcome parameters (e.g. the incidence of death or chronic lung disease at 36 weeks, intraventricular haemorrhage grade 3 or 4 or periventricular leucomalacia) [4]. Unfortunately, it is then concluded that a particular intervention does not have a role in the field of neonatology. In our opinion this approach is often too crude and should be revisited. Being born as a very premature infant constitutes a medical emergency with numerous medical problems, possibly occurring simultaneously (surfactant deficiency, patent ductus arteriosus, metabolic dysfunction, intraventricular haemorrhage, etc.). Therefore, it is unlikely for a single intervention (e.g. use of diuretics or permissive hypercapnia to prevent chronic lung disease) to impact significantly on crude outcome parameters. Deducing that these interventions have no place in neonatology would be short-sighted as they may very well have shown a positive trend [3]. In the future, clinical studies in neonatology should also assess a “compound” interventional approach, e.g. a lung protective approach (e.g. permissive hypercapnia plus use of diuretics, plus fluid restriction) vs a conventional approach. These studies should combine two or more interventions that have proved to be partially beneficial (positive trend) and assess prospectively whether the combination of these interventions will improve outcome parameters in the premature infant. These studies will have the potential to contribute more substantially to our knowledge in the complex field of neonatology and impact more profoundly on our therapeutic approach than studies that assess single interventions alone.

Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung

permissive hypercapnia, a stretch-limiting ventilation strategy, often results in high Pa(CO(2)). This strategy is associated with reduced morbidity and mortality in premature infants and its benefits have been attributed to diminished barotrauma. However, little is known about the independent effect of high CO(2) levels during the lung development. mice were exposed to 8% CO(2) or room air for 2 wk either from postnatal day 2 through 17 or as adults (approximately 2 mo of age). Lungs were excised and processed for protein, RNA, histology, and total lung volumes. histologic analysis demonstrated that alveolar walls of CO(2)-exposed mouse pups were thinner than those of controls and had twice the total lung volume. Molecular analysis revealed that several matrix proteins in the lung were downregulated in mouse pups exposed to hypercapnia. Interstitial collagen type I alpha1, type III alpha1, elastin and fibronectin protein, and mRNA levels were less than half of controls while collagen IV alpha 5 was unaffected. This decrease in interstitial collagen could thus account for the thinning of the interstitial matrix and the altered lung biomechanics. Matrix metalloproteinase (MMP)-8, a collagenase that has specificity for collagen types I and III, increased in hypercapnic mouse pups, suggesting increased collagen degradation. Moreover, tissue inhibitor of MMP (TIMP)-1, a potent inhibitor of MMP-8, was significantly decreased. However, unlike pups, adult mice exposed to hypercapnia demonstrated only a mild increase in total lung volumes and did not exhibit similar molecular or histologic changes. although permissive hypercapnia may prevent lung injury from barotrauma, our study revealed that exposure to hypercapnia may be an important factor in lung remodeling and function, especially in early life.

IntroductionBurn injuries significantly increase a patient’s metabolic demand. Adequate nutrition is essential to aid in recovery and reduce morbidity and mortality. This is important for pediatric patients, who have limited reserves and are in a period of growth, in contrast to adults. Burn patients often need multiple surgeries, with standard perioperative fasting periods leading to multiple nutritional interruptions. Continuous intraoperative feeding has been a proposed solution, but there is no current consensus on its role and safety, particularly in the pediatric population. The goal of our study was therefore to examine the safety and benefits of intraoperative nutrition in critically ill pediatric burn injury patients.MethodsA systematic review of MEDLINE, PubMed, Scopus, and Google Scholar was conducted using the following terms: Feeding or enteral or nutrition or fasting and adolescent or youth or pediatric or child or teen and burn or thermal injury or fire. The primary outcome was incidence of aspiration. Secondary outcomes included patient nutritional status (caloric deficit, weight), wound healing, days spent in the intensive care unit, ventilator days, pneumonia, number of surgeries, length of hospital stay, and mortality. Pooled analyses of binary outcomes were computed.ResultsFour studies consisting of 496 patients, met inclusion criteria. All studies were level IV evidence, but had high methodological quality. The median burn total body surface area (TBSA) was 43.8% (IQR 33.4-58.8%), with a median of one-third of patients having an inhalational injury. Patients underwent a median of 4.2 surgeries (IQR 1.8-7.4). Intraoperative feeding was conducted through nasoduodenal tubes. There were no aspiration events. Pooled analysis demonstrated that there were no differences in rates of aspiration, pneumonia, or wound infection (p >0.05) between patients who were intraoperatively fed and those who were not. Those fed intraoperatively had significantly more surgeries, ventilator days, longer hospital stays, but lower mortality (p< 0.05). There was large heterogeneity in nutritional assessment methods. Intraoperatively fed patients had an average gain of 144.4 kcal/kg and 1.7 days of exclusive enteral nutrition (vs. loss of -119.1 kcal/kg and -1.4 days) and cumulative positive caloric balance of +2673kcal ±2147 (vs. loss of -7899kcal ±3123), compared to those with interrupted feeding.ConclusionsContinuous intraoperative duodenal feeding during burn surgery appears to be safe in the Pediatric burn population, with no reported episodes of aspiration. Uninterrupted feeding was also associated with weight maintenance and reduced caloric deficit. It may also have survival benefit, as continuously fed patients needed more surgeries and intensive/hospital care, but had decreased mortality.

Introduction Children under the age of five years are particularly vulnerable to scalds and contact burns and have the highest rate of hospitalization and mortality from burns. Studies of costs associated with pediatric burns have included a limited number of patients and focused on inpatient and complication costs, limiting our understanding of the full economic burden of pediatric burns, including costs incurred through outpatient care and caregivers’ productivity loss. This study aimed to develop a societal costing model for burn injuries among children aged 0 to 4 years. Methods Children aged 0 to 4 years identified through the local Burn Registry with a burn injury between January 1, 2014 and March 15, 2018 were included in this study. Patients with inhalation injury, electrical, chemical and friction burns were excluded. An incidence-based cost-of-illness analysis with a human capital approach was used to quantify the cost of partial and full-thickness burns according to the percentage of total body surface area (%TBSA) involved. The cost of a burn injury was assessed from a societal perspective through the following cost categories: emergency department visits, inpatient, outpatient dressing changes, outpatient burnbaths, day surgeries, clinic visits and caregiver productivity losses. A list of resource items for each category were extracted from patient chart review, the local Burn Registry, and the local Hospital Finance Database, and assigned unit prices. Costs were discounted to a present value in 2017 dollars at 1.5% per annum. Results Burn injuries were observed for 342 children, of which 249 (73%) had their burn severity classified (%TBSA and partial/full thickness) and were included in this study. Burn severity categories (1–5%, 6–10%, 11–20%, and &amp;gt;20%) were developed based on the differential distribution of the costs allocated to each burn incident. The majority of children (60.8%) suffered from a 1–5% burn. A 1–5%, 6–10%, 11–20%, and &amp;gt;20% burn respectively cost an average of $2,229, $8,653, $13,663, and $98,634 to society. Costs incurred by the 1–5% burns were related mostly to emergency department visits and dressing changes, while costs incurred by the &amp;gt;20% were related mostly to inpatient and clinic visits (garments) costs. Conclusions This costing approach raises awareness about the important, yet preventable economic burden that pediatric burn injuries place on society. Applicability of Research to Practice This evidence may persuade policymakers and clinicians to invest in pediatric burns prevention programs in order to decrease pediatric burns costs allowing for the allocation of funds towards other clinical initiatives. This costing model may also facilitate cost-effectiveness analyses of burn prevention programs in the coming years.

Percutaneous mesh expansion

PCT levels could distinguish sepsis in children with burn injuries, performing better than CRP levels. Confirmatory studies are needed to evaluate the development of sepsis and the role of PCT in diagnosing sepsis in pediatric burn patients. • Even though there are excellent criteria for the diagnosis of infection and sepsis in children and several clinical parameters and biomarkers are being studied, it's difficult to diagnose burn wound sepsis in children. • Data from this study showed that procalcitonin levels performed better than CRP levels as a biomarker for distinguishing sepsis from systemic inflammatory response syndrome (SIRS) in children with burn injuries.