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Humans are critically dependent on the cardiorespiratory control system for adequate uptake of oxygen and removal of CO2 via lungs. (Dahan et al., 2010) Oxygen is required for each cell of the body to carry out its function and as a result, carbon dioxide, which is the waste product of many chemical reactions, is formed in our body, which is then excreted out with the help of ventilation.


Ventilation is controlled by two systems:

1. Chemical or metabolic control of breathing

2. Behavioral control system.


Opioids are used for the treatment of acute and chronic pain and play an important role in sedative care. Furthermore, these prescription opioids often change hands, resulting in misuse and abuse outside of the medical setting with casualties from an overdose or dangerous drug combinations (for example, opioids combined with sedatives, alcohol).


Recently, the number of individuals die from prescription opioids are more than the number of people die from illicit drugs e.g. heroin and cocaine. In America, the amount of prescription opioid overdose deaths increased from 4,400 in 1999 (12 people/day) to 16,000 in 2010 (44 people/day). Over this same period, there were similar increases in opioid sales (more than 4 million Americans per year receive long-acting or prolonged-release opioids for the treatment of chronic pain) and admissions in opioid-abuse treatment centers (>400%). (Volkow et al., 2014) The increase in opioid prescribing in the United States is related to the greater awareness of doctors and to the high rate of opioid formulations being marketed, and to the pressure from the industry on physicians to prescribe opioids. Although we have a good idea of the number of individuals who die from prescription opioids, the number of near-fatal events remains unknown. In agreement with the data from the community, parenteral (oral) opioids in the clinical setting are considered a major and independent risk factor for the development of cardiorespiratory arrest. (Davies et al., 2009)


Since opioid receptors are abundant in brainstem respiratory centers, (Pattinson, 2008) various opioid-related effects are observed:

1. Depression of the ventilatory responses to hypercapnia and hypoxia

2. Depression of ventilation (related to reductions in respiratory rate and volume) and the wakefulness drive to breathe

3. Irregular breathing

4. Suppression of pharyngeal muscle (including the tongue) function

5. Depression of the arousal response.


· Opioid dose

· Route of administration

· The speed at which the opioid concentration rises at its site of action (for example, a slow rise enables the patient to accumulate CO2 which offsets OIRD) (Olofsen et al., 2010)

· Underlying disease (for example, recurrent hypoxic events enhance opioid sensitivity). (Brown et al., 2006)

· Inspired oxygen concentration (a high fraction of inspired oxygen [FiO2] enhances OIRD – Figure 1) (Moss et al., 2006)

· Genetics and gender

The clinical picture emerges, relates to the complex interactions with brain sites that is involved in arousal, nociception, nausea/vomiting, and so on. Some patterns of OIRD are dominated by

· Superficial ventilation

· Reduced respiratory rates and eventually central apnea

· Others by cyclic breathing and obstructive events.


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