Project Summary According to the Center for Disease Control (CDC), there has been an upward trend in the number of opioid- related deaths, with a total of nearly 600,000 deaths during the period 1999 to 2019. In 2021, the CDC determined that opioid overdose deaths rose significantly amongst blacks, especially black males. Despite the apparent solution of administering naloxone to opioid-overdosed individuals to reverse the respiratory depression, many people still died because naloxone was not administered in a timely manner. Therefore, timely detection of respiratory depression and automatic administration of the drug naloxone to individuals who have overdosed on opioids is the key to saving their lives. Although arterial blood gas measurement remains the gold standard for guiding respiratory management, the necessity for placement of indwelling arterial lines or intermittent arterial or heel blood sampling makes it inapplicable for home testing. Transcutaneous monitors were introduced in the 1970s to measure the transcutaneous CO2 partial pressure (tcpCO2) that approximated the arterial value when the skin underneath the sensor was heated to 42-44°C. Disadvantages include potential for skin burns, frequent sensor site changes and re-calibrations. TcpCO2 monitoring is more accurate than end-tidal CO2 monitoring in patients with shunt or ventilation-perfusion inequalities and can be used in situations such as high frequency or non-invasive ventilation where end-tidal CO2 monitoring cannot. Although traditional transcutaneous monitors have the advantage of non-invasive measurement, the measurement needs a 15-20-minute heating period to reach stable values despite raising the skin temperature to 42C or higher. In addition, these devices are large and expensive (~$25,000), making them also inapplicable for personal use. In order to stem the opioid crisis, we propose early detection of respiratory depression by continuous monitoring of transcutaneous CO2. This will help with the prevention and treatment of communities that have been disproportionately affected by opioid overdose deaths. The monitor is based on the CO2 transdermal diffusion rate and will be applied non- invasively on the patient's arm. It can quickly detect opioid overdose-induced respiratory depression, which can then enable an automatic administration of the drug naloxone in a timely manner, thus optimizing the patient's survival. The prototypes will be tested with 20~50 subjects to determine the safety, accuracy, and side effects, if any, after long-term of continuous use. Animal studies will be conducted to see if the device can pick up the blood CO2 changes induced by morphine injection.