In the fast-paced world of sports medicine and rehabilitation, the quest for faster recovery from injuries drives continuous innovation in therapeutic approaches. Strains and sprains represent some of the most common musculoskeletal injuries, affecting everyone from elite athletes to weekend warriors. Traditional treatment methods, while effective, often require weeks or even months for complete recovery, leaving patients frustrated and eager for alternatives. Enter CO₂ cryotherapy—a cutting-edge treatment that promises to revolutionize injury recovery through the precise application of extremely cold carbon dioxide. This advanced therapeutic modality claims to accelerate healing, reduce pain, and restore function faster than conventional methods, but does the science support these bold claims?
Introducción
Understanding the potential of CO₂ cryotherapy requires examining both the nature of common soft tissue injuries and the evolving landscape of therapeutic interventions designed to optimize recovery outcomes. This comprehensive analysis will explore whether this innovative treatment truly lives up to its promise.
What Are Strains and Sprains?
Strains and sprains represent distinct categories of soft tissue injuries that affect different anatomical structures but share similar pathophysiological mechanisms. A strain occurs when muscle fibers or tendons are overstretched or torn, typically resulting from sudden forceful contractions, eccentric loading, or muscle fatigue. These injuries affect the muscle-tendon unit and can range from microscopic fiber disruption (Grade I) to complete rupture (Grade III). Sprains involve damage to ligaments—the fibrous connective tissues that connect bone to bone—caused by joint movement beyond normal range of motion. Like strains, sprains are classified by severity, with Grade I involving mild stretching, Grade II partial tearing, and Grade III complete ligament rupture. Both injury types trigger inflammatory cascades, tissue damage, and functional impairment requiring targeted therapeutic intervention.
Why Recovery Speed Matters for Athletes and Active Individuals
The speed of recovery from strains and sprains has profound implications for athletic performance, career longevity, and quality of life for active individuals. Professional athletes face tremendous pressure to return to competition quickly, as extended absence can impact team dynamics, contract negotiations, and career trajectories. Amateur athletes and fitness enthusiasts also prioritize rapid recovery to maintain training consistency, prevent deconditioning, and preserve motivation for continued participation. Prolonged recovery periods increase the risk of secondary complications including muscle atrophy, joint stiffness, cardiovascular deconditioning, and psychological impacts such as depression and anxiety. Furthermore, delayed healing can lead to compensatory movement patterns that predispose individuals to additional injuries. The economic implications are substantial, with lost work productivity, healthcare costs, and potential long-term disability creating significant financial burdens for individuals and society.
The Rise of CO₂ Cryotherapy in Sports Medicine
CO₂ crioterapia has emerged as a revolutionary therapeutic modality in sports medicine, gaining popularity among professional teams, rehabilitation centers, and performance optimization clinics worldwide. This advanced form of cryotherapy utilizes pressurized carbon dioxide delivered at extremely low temperatures to create targeted therapeutic effects that surpass traditional ice application methods. The technology has evolved from laboratory settings to clinical practice, with increasing adoption driven by promising preliminary results and athlete testimonials. Unlike whole-body cryotherapy chambers, CO₂ cryotherapy allows for precise localized treatment, making it ideal for addressing specific injury sites. The treatment’s growing reputation stems from its ability to provide immediate pain relief, reduce inflammation, and potentially accelerate the healing process through sophisticated physiological mechanisms. As research continues to emerge, sports medicine practitioners are increasingly incorporating CO₂ cryotherapy into comprehensive treatment protocols for acute and chronic musculoskeletal conditions.
Understanding Strains and Sprains
To fully appreciate how CO₂ cryotherapy might enhance healing, we must first understand the complex pathophysiology of strains and sprains, including their underlying mechanisms, clinical presentations, and natural healing processes. This foundation is crucial for evaluating therapeutic interventions.
Difference Between Muscle Strains and Ligament Sprains
| Característica | Muscle Strains | Ligament Sprains |
| Anatomical Structure Affected | Muscle fibers (actin, myosin) and connective tissue matrices (endomysium, perimysium, epimysium) | Ligaments composed of type I collagen |
| Vulnerable Site | Muscle–tendon junction | Ligament midsubstance with limited vascularity |
| Mechanism of Injury | Typically during eccentric contractions with forced muscle lengthening | Excessive tensile load or abnormal joint movement |
| Biomechanical Properties | Contractile tissue with high adaptability to load | Non-contractile tissue with tensile strength and viscoelasticity |
| Healing Capacity | Relatively better vascular supply supports recovery | Limited vascularity slows repair and prolongs recovery |
Common Causes: Sports Injuries, Overuse, Poor Conditioning
- Sudden directional changes, jumping, landing, or direct impacts can exceed tissue tolerance and cause acute injuries.
- Overuse injuries result from repetitive microtrauma that outpaces tissue repair capacity.
- Poor conditioning, including muscle imbalances, low flexibility, and weak neuromuscular control, increases injury risk.
- Environmental factors such as surface conditions, equipment design, and weather can influence likelihood of injury.
- Biomechanical abnormalities like leg length discrepancies, foot pronation, or altered movement mechanics create abnormal stress loads.
- Previous injuries, inadequate rehab, and premature return to activity significantly raise the risk of reinjury.
Symptoms That Indicate Strains or Sprains
- Sharp, localized pain or a tearing/popping sensation often occurs at the moment of injury.
- Rapid swelling develops due to vascular permeability and inflammatory mediator release.
- Bruising may appear within hours or days, showing color changes from red to purple to yellow-green.
- Muscle strains typically present with tenderness, spasm, and weakness during stressed movements.
- Sprains often cause joint instability, reduced range of motion, and pain during weight-bearing.
- Functional testing may reveal strength loss, proprioceptive deficits, and compensatory movement patterns.
- Severe injuries can present with deformity, total loss of function, or inability to bear weight.
Typical Healing Timeline Without Intervention
The natural healing process for strains and sprains follows predictable phases with specific cellular and molecular events that determine recovery timelines and functional outcomes. The inflammatory phase (0-72 hours) begins immediately with hemostasis, platelet aggregation, and inflammatory cell recruitment including neutrophils, macrophages, and lymphocytes. Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) orchestrate the initial response while simultaneously initiating tissue repair mechanisms. The proliferative phase (3-21 days) involves fibroblast migration, collagen synthesis, angiogenesis, and granulation tissue formation. Type III collagen predominates initially, providing temporary structural support but lacking the strength of mature tissue. The remodeling phase (21 days to 6+ months) features collagen maturation, cross-link formation, and tissue reorganization along lines of mechanical stress. Grade I injuries typically resolve within 2-6 weeks, Grade II injuries require 6-12 weeks, while Grade III injuries may need 3-6 months or longer for complete healing.
¿Qué es la crioterapia de CO₂?
Understanding the technology and mechanisms behind CO₂ cryotherapy is essential for evaluating its therapeutic potential in treating strains and sprains. This section explores the scientific foundation and practical applications of this innovative treatment modality.
What Is CO₂ Cryotherapy? Definition and Benefits
CO₂ cryotherapy represents an advanced therapeutic technique that utilizes pressurized carbon dioxide gas to deliver controlled, localized cooling at extremely low temperatures reaching -78°C (-108°F). The treatment applies controlled bursts of carbon dioxide directly to affected areas, creating rapid thermal shock through pressurized gas delivery that triggers immediate vasoconstriction and reduces metabolic demand in treated tissues. Unlike traditional cryotherapy methods, CO₂ cryotherapy provides precise temperature control and targeted application, allowing practitioners to customize treatment parameters based on specific injury characteristics and patient needs. The system operates through specialized delivery devices that regulate pressure, temperature, and application duration to optimize therapeutic outcomes. Treatment sessions typically last 10-15 seconds per application site, with the extreme cold creating immediate physiological responses including pain relief, inflammation reduction, and enhanced circulation. The precision and intensity of CO₂ cryotherapy enable more targeted therapeutic effects compared to conventional ice applications.
How CO₂ Cryotherapy Differs from Ice Packs and Whole-Body Cryotherapy
The fundamental differences between CO₂ cryotherapy and traditional cooling methods lie in temperature precision, application control, and therapeutic penetration depth. Conventional ice packs typically achieve temperatures between 0-10°C (32-50°F) and require 15-20 minutes of application to achieve therapeutic effects, often causing skin irritation and uneven cooling patterns. CO₂ cryotherapy delivers rapid thermal shock at -78°C, creating immediate vasoconstriction followed by reactive vasodilation that accelerates oxygen and nutrient delivery to damaged tissues. Whole-body cryotherapy chambers expose the entire body to temperatures around -110°C to -140°C for 2-4 minutes, creating systemic effects but lacking the precision needed for targeted injury treatment. CO₂ cryotherapy combines the intensity of extreme cold with localized precision, allowing practitioners to treat specific anatomical structures without affecting surrounding healthy tissue. The controlled application duration prevents tissue damage while maximizing therapeutic benefits through optimal physiological response activation.
Mechanism of Action: Extreme Cold, Vasoconstriction, and Vasodilation
The therapeutic mechanisms of CO₂ cryotherapy rely on physiological responses to extreme cold that promote tissue healing and pain relief. Exposure to CO₂ rapidly induces vasoconstriction, reducing blood flow, metabolic demand, and secondary damage from inflammatory processes. The sudden cooling activates thermoreceptors and nociceptors, triggering neurological responses that relieve pain through the gate control theory. After the initial vasoconstriction, reactive vasodilation occurs, producing a “pumping effect” that enhances circulation, improves nutrient delivery, and accelerates the removal of waste products. This alternating vascular response creates favorable conditions for tissue repair. Additionally, cold exposure reduces inflammatory mediator activity and metabolic enzyme function, limiting hypoxic damage to surrounding healthy tissues. By lowering oxygen consumption and modulating cellular metabolism, CO₂ cryotherapy protects injured tissues during critical early stages of healing. Together, these mechanisms explain its effectiveness in reducing pain, controlling inflammation, and promoting recovery from musculoskeletal injuries.
How CO₂ Cryotherapy Helps with Strains and Sprains
The therapeutic benefits of CO₂ cryotherapy for strains and sprains stem from its ability to address multiple aspects of injury pathophysiology simultaneously. Understanding these mechanisms helps explain why this treatment shows promise for accelerating recovery.
Reducing Inflammation and Swelling at the Injury Site
CO₂ cryotherapy reduces inflammation and swelling by targeting vascular and cellular mechanisms within the inflammatory response. Extreme cold triggers immediate vasoconstriction of blood vessels and lymphatics, limiting fluid leakage and preventing excessive edema at the injury site. This vascular effect also restricts the accumulation of inflammatory mediators and immune cells that intensify pain and tissue damage. On a cellular level, cryotherapy modulates cytokine activity by lowering pro-inflammatory markers like TNF-α and IL-1β while enhancing anti-inflammatory responses. The cooling process reduces metabolic demand, decreasing oxygen consumption and minimizing secondary hypoxic injury to healthy surrounding tissues. It further stabilizes membrane permeability and ion channel function, reducing cellular swelling and preserving structural integrity. Additionally, the rapid temperature shift activates thermoregulatory responses that support the healing cascade, creating an environment that controls harmful inflammation while promoting tissue repair and recovery.
Pain Relief Through Neural Desensitization
The analgesic effects of CO₂ cryotherapy result from sophisticated interactions with peripheral and central nervous system pain processing mechanisms. Extreme cold application directly affects nociceptor function through temperature-sensitive ion channels, particularly TRPM8 (cold and menthol receptor 1) and TRPA1 (transient receptor potential ankyrin 1) channels that modulate pain signal transmission. The rapid temperature change creates a strong sensory input that activates large-diameter A-β nerve fibers, which according to the gate control theory, inhibit smaller pain-transmitting C-fibers at the spinal cord level. Cold-induced nerve conduction velocity changes reduce the speed and intensity of pain signal transmission to the brain, providing immediate relief. The treatment also triggers the release of endogenous opioids including endorphins and enkephalins, which provide centrally-mediated analgesia. Local anesthetic effects occur through direct neural membrane stabilization and reduced nerve excitability. These combined mechanisms create immediate and sustained pain relief that facilitates early mobilization and functional recovery.
Enhancing Circulation and Oxygen Delivery for Faster Healing
CO₂ cryotherapy enhances circulation to create optimal conditions for tissue healing by improving perfusion and nutrient delivery. Alternating vasoconstriction and vasodilation generate a “pumping” effect that drives more efficient blood flow compared to static cold therapies. This mechanism increases oxygen, glucose, amino acid, and nutrient delivery essential for cellular repair while accelerating the removal of metabolic waste, inflammatory debris, and damaged tissue components. Improved circulation supports angiogenesis, enabling the growth of new blood vessels necessary for sustaining perfusion in regenerating tissue. Cryotherapy also stimulates lymphatic drainage, reducing congestion and clearing excess fluids and inflammatory mediators. By improving immune cell trafficking, particularly macrophage activity, the therapy accelerates damaged tissue clearance while promoting repair and regeneration. Together, these effects create a balanced vascular and cellular environment that not only reduces inflammation but also supports long-term functional recovery.
Supporting Tendon, Ligament, and Muscle Tissue Repair
CO₂ cryotherapy aids the repair of soft tissue structures by enhancing cellular metabolism, protein synthesis, and tissue remodeling. The treatment stimulates fibroblast activity and collagen synthesis, restoring the structural integrity of tendons and ligaments. Increased ATP production provides the energy needed for protein synthesis, cellular division, and repair processes. Collagen fibers are organized along lines of stress, improving the biomechanical strength of healing tissues. In muscle, cryotherapy activates satellite cells and supports myofiber regeneration, facilitating recovery of damaged contractile elements. The therapy regulates matrix metalloproteinase (MMP) activity, balancing tissue breakdown and synthesis during remodeling. It also helps restore muscle function by reducing neuromuscular fatigue, enabling a faster return to activity. Additionally, growth factor release and signaling pathway activation promote comprehensive tissue repair and functional restoration across tendons, ligaments, and muscle. Together, these effects establish cryotherapy as a valuable tool for accelerating recovery and strengthening soft tissue healing.
Pruebas clínicas y opiniones de expertos
Evaluating the effectiveness of CO₂ cryotherapy requires careful analysis of available research evidence and expert perspectives from sports medicine practitioners. This section examines the current state of scientific support for this therapeutic approach.
Key Research Studies on Cryotherapy for Sports Injuries
Clinical research on cryotherapy for sports injuries shows both benefits and limitations. Most studies report positive effects on pain reduction and short-term recovery, but many trials have methodological weaknesses that limit strong conclusions. Current evidence does not confirm that cryotherapy prevents secondary tissue damage or directly promotes tissue regeneration, despite its clear analgesic effects. For example, studies suggest that traditional ice therapy with compression may not provide significant advantages over no cryotherapy in ankle sprains when measuring pain, swelling, and range of motion. Systematic reviews highlight that treatment duration and protocol consistency are key factors influencing outcomes, yet these vary widely across studies. In contrast, newer research on CO₂ cryotherapy has produced more promising findings. Studies show that CO₂-based methods may enhance circulation, accelerate muscle function recovery, and deliver more consistent benefits than traditional ice applications, making it a growing focus in sports medicine.
Evidence Supporting CO₂ Cryotherapy for Accelerated Recovery
Emerging research highlights the advantages of CO₂ cryotherapy over traditional cooling methods for injury recovery and performance enhancement. Clinical studies have shown that CO₂ cryotherapy provides greater improvements in pain reduction, functional capacity, and return-to-activity times compared to standard ice therapy. Research also suggests that CO₂ cooling enhances immediate muscle recovery from neuromuscular fatigue, offering unique benefits for athletes seeking faster performance restoration. Localized CO₂ applications have been linked to reduced inflammation markers, improved joint range of motion, and quicker functional recovery when compared to conventional treatments. Patient-reported outcomes frequently indicate higher satisfaction and perceived effectiveness with CO₂ cryotherapy. Objective measures, such as thermography, ultrasound, and biomechanical testing, also demonstrate superior tissue healing responses with CO₂ treatment. Despite these promising findings, CO₂ cryotherapy is still a relatively new modality, and long-term studies with large patient populations are needed to confirm its efficacy and safety in sports medicine.
How Sports Physicians and Physical Therapists Use CO₂ Cryotherapy
Sports medicine practitioners are increasingly integrating CO₂ cryotherapy into treatment protocols for both acute and chronic musculoskeletal conditions. Physical therapists often combine CO₂ cryotherapy with manual therapy, exercise programs, and patient education to maximize recovery outcomes. Sports physicians recommend it as an immediate post-injury intervention, particularly for competitive athletes who need rapid return-to-play solutions. Beyond injury care, CO₂ cryotherapy is also used in pre-competition routines to improve muscle readiness and in post-competition recovery to reduce soreness and speed healing. Clinicians report positive results for conditions such as muscle strains, ligament sprains, tendinopathies, and overuse injuries. Typical protocols involve multiple sessions across days or weeks, with treatment intensity and frequency adjusted to the severity of injury and patient response. Many practitioners enhance results by combining CO₂ cryotherapy with complementary modalities like compression therapy, electrical stimulation, and therapeutic ultrasound, creating a synergistic approach that supports faster and more complete musculoskeletal recovery.
Limitations and Areas Requiring Further Research
Despite encouraging early findings, CO₂ cryotherapy research remains limited and requires more robust investigation. Current scientific evidence is largely anecdotal due to the scarcity of randomized controlled trials, a gap that extends specifically to CO₂ cryotherapy applications. Standardization of treatment protocols—including ideal temperature, duration, frequency, and timing—has not yet been established and must be addressed in future studies. Long-term safety and potential adverse effects remain underexplored, particularly for repeated use or in vulnerable populations. Although proposed mechanisms of action are theoretically sound, they need validation through laboratory research and clinical trials using objective outcome measures. Cost-effectiveness comparisons with conventional therapies are also necessary to inform healthcare decision-making and insurance policies. Further research should focus on identifying optimal patient selection criteria, contraindications, and predictors of treatment response. Ultimately, large-scale, multi-center randomized controlled trials with extended follow-up are essential for developing evidence-based clinical guidelines.
Who Can (and Can’t) Benefit from CO₂ Cryotherapy?
Understanding appropriate patient selection for CO₂ cryotherapy is crucial for optimizing treatment outcomes and ensuring patient safety. This section outlines ideal candidates and important contraindications for this therapeutic approach.
Ideal Candidates (Athletes, Active Adults, Chronic Cases)
- Elite and recreational athletes benefit from faster recovery and pain relief that supports consistent training and competition.
- Active adults engaged in sports, exercise, or demanding occupations can use cryotherapy to manage acute injuries and prevent chronic issues.
- Individuals with chronic pain conditions, such as recurrent strains or persistent joint discomfort, may find significant relief.
- Patients unresponsive to conventional treatments like ice therapy, medication, or physical therapy may improve with CO₂ cryotherapy.
- Those seeking drug-free, non-invasive pain management options appreciate its minimal side effects and safety profile.
Contraindications (Who Should Avoid Treatment)
- People with cold allergies, cryoglobulinemia, or cold urticaria risk severe allergic reactions.
- Patients with circulatory disorders such as peripheral vascular disease or Raynaud’s phenomenon face tissue damage risks.
- Pregnant women should avoid CO₂ cryotherapy due to unknown effects on maternal and fetal health.
- Open wounds, infections, or compromised skin increase the risk of worsening injury or infection.
- Individuals with severe cardiovascular disease, uncontrolled hypertension, or recent cardiac events may face harmful stress responses.
- Patients with neuropathy or reduced sensation cannot safely detect cold-related injury.
When It Might Not Be the Best Option
- Acute injuries in the first 24–48 hours may benefit more from gentle cooling and rest rather than intense CO₂ cryotherapy.
- Severe ligament tears, tendon ruptures, or fractures requiring surgical repair should be treated with appropriate medical interventions first.
- Patients with low tolerance to extreme cold, including those with anxiety or discomfort about cryotherapy, may prefer alternative treatments.
- People expecting instant results may be disappointed, as benefits often occur gradually over multiple treatments.
Post-Treatment Care and Recovery Tips
Optimizing CO₂ cryotherapy outcomes requires comprehensive post-treatment care and strategic recovery planning. This section provides evidence-based recommendations for maximizing therapeutic benefits and supporting the healing process.
Gentle Stretching and Mobility After Cryotherapy
Post-cryotherapy mobility work should begin immediately once pain decreases and tissue pliability improves. Gentle range of motion exercises maintain joint mobility and prevent stiffness after injury and cold exposure. Stretching should be progressive, emphasizing pain-free movements and avoiding techniques that stress healing tissues. Performing dynamic warm-ups before stretching helps restore tissue temperature and prepares muscles for activity. Proprioceptive exercises that challenge balance and coordination aid in restoring neuromuscular control and reducing re-injury risk. Prioritizing movement quality over quantity ensures proper biomechanics and motor patterns. Patients should monitor their response, adjusting intensity according to comfort and symptoms. The analgesic effects of CO₂ cryotherapy provide an optimal window for therapeutic exercise, which should be strategically used to maximize recovery benefits.
Nutrition and Hydration to Support Tissue Healing
Optimal nutrition and hydration are essential for supporting tissue repair after CO₂ cryotherapy. Adequate protein intake (1.2–2.0 g/kg body weight) provides amino acids necessary for collagen synthesis and muscle repair, especially during the proliferative healing phase. Anti-inflammatory nutrients—omega-3 fatty acids, vitamins D and C, and polyphenols—help regulate inflammation and promote tissue regeneration. Proper hydration supports cellular function, circulation, nutrient transport, and waste removal. Timing meals around treatment, particularly those rich in antioxidants post-session, may enhance recovery. Key micronutrients, including zinc, copper, and vitamin A, play specific roles in wound healing and collagen formation and should be maintained at optimal levels. Avoiding pro-inflammatory foods or substances, such as excessive alcohol and processed foods, further supports recovery. Individual nutritional strategies should be tailored to injury severity, activity level, and metabolic demands to maximize the therapeutic benefits of cryotherapy.
Rest vs. Active Recovery — Finding the Balance
Balancing rest and activity after CO₂ cryotherapy depends on injury severity, healing phase, and individual tolerance. Complete rest may be necessary immediately after severe injuries to prevent further damage and allow initial healing. However, early gentle mobilization often leads to better outcomes than prolonged immobilization for most strains and sprains, especially when pain is controlled by cryotherapy. Active recovery—including light aerobic activity, gentle movement, and therapeutic exercises—supports circulation, prevents deconditioning, and aids healing. Activity progression should be guided by pain, noting that cryotherapy’s analgesic effects can mask symptoms. Sleep quality and duration (7–9 hours) are critical for tissue repair and inflammation resolution. Gradual return to normal activities based on functional milestones rather than time alone reduces re-injury risk. Professional guidance ensures the rest-activity balance is tailored to individual circumstances, optimizing recovery and long-term outcomes.
Combining Cryotherapy with Rehabilitation Exercises
Integrating CO₂ cryotherapy with rehabilitation exercise programs enhances overall recovery outcomes. Pre-exercise cryotherapy reduces pain and muscle guarding, allowing more effective therapeutic exercise and improved movement quality. Post-exercise cryotherapy helps control inflammation and soreness from tissue loading during rehabilitation. Progressive loading protocols should gradually challenge healing tissues while using cryotherapy to manage symptoms and support recovery. Functional movement training alongside cryotherapy restores sport- or activity-specific patterns needed for full participation. Strength training should progress systematically, with cryotherapy aiding tissue adaptation and recovery between sessions. Proprioceptive and neuromuscular control exercises benefit from pain reduction and increased mobility provided by cryotherapy. Optimizing treatment timing and sequencing maximizes the therapeutic window created by cryotherapy’s analgesic and anti-inflammatory effects, supporting efficient rehabilitation and reducing the risk of re-injury.
Final Verdict: Can CO₂ Cryotherapy Really Speed Up Healing?
CO₂ cryotherapy shows significant promise for treating strains and sprains, though definitive proof of accelerated healing requires further research. Its immediate pain relief, inflammation reduction, and enhanced circulation create favorable conditions for tissue repair, potentially supporting faster recovery. Clinical studies report positive effects on pain reduction and neuromuscular recovery, with emerging evidence suggesting CO₂ cryotherapy may offer advantages over traditional cooling methods. Physiologically, its mechanisms—vasoconstriction followed by reactive vasodilation, reduced metabolic demand, and improved nutrient delivery—provide a strong theoretical basis for its therapeutic effects. Rapid thermal shock and circulation enhancement create optimal conditions for tissue healing. However, research is limited by few high-quality randomized trials and largely anecdotal evidence, leaving long-term safety and protocol standardization areas for future study. For patients seeking non-invasive, drug-free options, CO₂ cryotherapy is a promising adjunct to rehabilitation. It likely accelerates pain relief and early functional recovery, enhancing patient outcomes while maintaining an excellent safety profile.
