Respiratory Depression

Cortex recently undertook a marketing research study performed by VPMR, LLC. VPMR LLC is the former Verispan Primary Market Research Division, a renowned health care information company. VPMR’s clients include many of the Top 50 pharmaceutical companies, several leading biotech and medical/surgical companies, consulting firms, and other health care related organizations. 

The three phases of this research involved a Qualitative Phase with a broad selection of surgical specialties, anesthesiologists, pulmonologists and nurse anesthetists. Individuals were interviewed to get an impression of their understanding of respiratory depression, its current management and perceived needs to improve outcomes.  Once these interviews were collected and analyzed, an additional 200 surgeons and anesthesiologists were interviewed across the United States. Questionnaires were designed to gain information on the occurrence, existing treatments and general attitudes regarding the level of satisfaction of physicians that deal with post-surgical respiratory depression induced by opiate analgesics, sedative anesthetics and benzodiazepines. 

Main Findings

Respiratory depression (RD).is a state of hypoventilation in which there is a reduced amount of air entering the lungs, resulting in significant change in respiratory rate and depth from baseline values.  RD requiring intervention is more dependent upon the patient’s clinical presentation and vital signs, including the following parameters:

• Mental status or alert state; if patient can be wakened
• Respiratory rate less than 8-10 breaths per minute
• Oxygen saturation is less than 90% on room air
• Arterial pCO2  >55 Hg or a 20% increase
• Specific anesthetics and analgesics given preoperatively, intra-operatively, and in the recovery room

Current management of respiratory depression

• Non-Pharmaceutical Management
  • Stimulate the patient
  • Support and protect airway
  • Oxygen mask
  • Supportive/assisted breathing
  • Endotracheal intubation
    
    
• Pharmaceutical Management/Treatment
  • Naloxone/Narcan® - reversal for opiates
  • Romazicon/Anexate (flumazenil) –reversal products for benzodiazepines (Versed)
    
    
• Utilization of Pharmaceutical Products
• The use of a pharmaceutical product to correct RD is preferred as a first line intervention due to less complications and cost associated with endotracheal intubation.
• Both Naloxone and Romazicon are frequently utilized
  Level of satisfaction with current treatments for respiratory depression
  
  
• Endotracheal Intubation
  • Highly effective, but, all healthcare providers wish to avoid this “extreme” intervention due to the negative impact on patient health, recovery time, and cost of care.
    
    
• Naloxone/Narcan®
  • Advantages
    • Effective, rapid, inexpensive and readily available
  • Disadvantages
    • Reverses opiates only
    • Reverses analgesic properties of pain medications
    • Need to wait several hours to re-dose pain medication
    • Significant side effects associated with its use including: pulmonary edema, increase in blood pressure or heart rate
    • If dosed too quickly in a large amount (bolus), it can induce respiratory depression or cardiac arrest

Although most available literature suggests that incidence of RD in the United States is <5%/ year, anesthesiologists in this study report that RD occurs in 15%/ year of surgical procedures

• Surgeons report a lower incidence of about 10%; orthopedic surgeons report the lowest incidence (7%), presumably given less invasive procedures (of extremities) not involving the thoracic region or requiring planned endotracheal intubation
• Both anesthesiologists and surgeons agree that patients who undergo planned endotracheal intubation experience RD more frequently than those who do not undergo intubation (12% vs. 8%, respectively)
• Furthermore, incidence was reported to be higher among inpatients (11%) compared with outpatients (5%)

Risk factors for Respiratory Depression

Elderly and sleep apnea are most frequently reported as risk factors for RD, other factors derived from this research can be seen on the chart below.   

VPMR conducted a Phase III Market Forecast to initially size the market for RD and obstructive sleep apnea prophylaxis, a logical extension but yet to be proved treatment in man.  Based on results of our questionnaires, VPMR estimates the US RD market size to be in excess of one billion dollars, as outline in the table below.