Epiduraland Intrathecal Opiate Analgesia

Small quantities of opioid injected intrathecally or epidurally produce segmental analgesia. Thus, spinal and epidural opioids are used in surgical procedures and for the relief of postoperative and chronic pain. As with local anesthesia, analgesia is confined to sensory nerves that enter the spinal cord dorsal horn in the vicinity of the injection. Presynaptic opioid receptors inhibit the release of substance P and other neurotransmitters from primary afferents, while postsynaptic opioid receptors decrease the activity of certain dorsal horn neurons in the spinothalamic tracts (see Chapters 6 and 21). Since conduction in autonomic, sensory, and motor nerves is not affected by the opioids, blood pressure, motor function, and non-nociceptive sensory perception typically are not influenced by spinal opioids. The volume-evoked micturition reflex is inhibited, as manifested by urinary retention. Other side effects include pruritus and nausea and vomiting in susceptible individuals. Delayed respiratory depression and sedation, presumably from cephalad spread of opioid within the CSF, occurs infrequently with the doses of opioids currently used.

Spinally administered opioids by themselves do not provide satisfactory anesthesia for surgical procedures. Thus, opioids have found the greatest use in the treatment of postoperative and chronic pain. In selected patients, spinal or epidural opioids can provide excellent analgesia following thoracic, abdominal, pelvic, or lower extremity surgery without the side effects associated with high doses of systemically administered opioids. For postoperative analgesia, spinally administered morphine, 0.2-0.5 mg, usually will provide 8—16 hours of analgesia. Placement of an epidural catheter and repeated boluses or an infusion of opioid permits an increased duration of analgesia. Many opioids have been used epidurally. Morphine, 2—6 mg, every 6 hours, commonly is used for bolus injections, while fentanyl, 20—50 ^g/hour, often combined with bupiva-caine, 5—20 mg/hour, is used for infusions. For cancer pain, repeated doses of epidural opioids can provide analgesia of several months' duration. The dose of epidural morphine, for example, is far less than the dose of systemically administered morphine that would be required to provide similar analgesia. This reduces the complications that usually accompany the administration of high doses of systemic opioids, particularly sedation and constipation. Unfortunately, as with systemic opioids, tolerance will develop to the analgesic effects of epidural opioids, but this usually can be managed by increasing the dose.

For a complete Bibliographical listing see Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th ed., or Goodman & Gilman Online at www.accessmedicine.com.

THERAPEUTIC GASES: O2, CO2, NO, AND He OXYGEN

Normal Oxygenation

Oxygen makes up 21% of air, with a partial pressure of 21 kPa (158 mm Hg) at sea level. The partial pressure drives the diffusion of oxygen; thus, ascent to elevated altitude reduces the uptake and delivery of oxygen to the tissues. As air is delivered to the distal airways and alveoli, the Po2 decreases by dilution with carbon dioxide and water vapor and by uptake into the blood. Under ideal conditions, when ventilation and perfusion are well matched, the alveolar Po2 will be -14.6 kPa (110 mm Hg). The corresponding alveolar partial pressures of water and CO2are 6.2 kPa (47 mm Hg) and 5.3 kPa (40 mm Hg), respectively. Under normal conditions, there is complete equilibration of alveolar gas and capillary blood. In some diseases, the diffusion barrier for gas transport may be increased; during exercise, when high cardiac output reduces capillary transit time, full equilibration may not occur, and the alveolar-end-capillary Po2 gradient may be increased.

The Po2 in arterial blood, however, is further reduced by venous admixture (shunt), the addition of mixed venous blood from the pulmonary artery, which has a Po2 of -5.3 kPa (40 mm Hg). Together, the diffusional barrier, ventilation-perfusion mismatches, and the shunt fraction are the major causes of the alveolar-to-arterial oxygen gradient, which is normally 1.3-1.6 kPa (10-12 mm Hg) when air is breathed and 4.0-6.6 kPa (30-50 mm Hg) when 100% oxygen is breathed.

Oxygen is delivered to the tissue capillary beds by the circulation and again follows a gradient out of the blood and into cells. Tissue extraction of oxygen typically reduces the Po2 of venous blood by an additional 7.3 kPa (55 mm Hg). Although the Po2 at the mitochondria is not known, oxidative phosphorylation can continue at a Po2 of only a few millimeters of mercury.

In the blood, O2 is carried primarily by hemoglobin and is to a small extent dissolved in solution. The quantity of O2 combined with hemoglobin depends on the Po2 (Figure 15-1). Hemoglobin is about 98% saturated with oxygen when air is breathed under normal circumstances, and it binds 1.3 mL of oxygen per gram when fully saturated. The steep slope of this curve with falling Po2 facilitates unloading of oxygen from hemoglobin at the tissue level and reloading when desat-urated mixed venous blood arrives at the lung. Shifting of the curve to the right with increasing temperature, increasing Pco2, and decreasing pH, as is found in metabolically active tissues, lowers the oxygen saturation for the same Po2 and thus delivers additional oxygen where and when it is most needed. However, the flattening of the curve with higher Po2 indicates that increasing blood Po2 by inspiring oxygen-enriched mixtures can increase the amount of oxygen carried by hemoglobin only minimally. Further increases in blood O2 content can occur only by increasing the amount of oxygen dissolved in plasma. Because of the low solubility of oxygen (0.226 mL/L/kPa or 0.03 mL/L/mm Hg at 37°C), breathing 100% O2 can increase the amount of O2 dissolved in blood by only 15 mL/L, less than one-third of normal metabolic demands. However, if the inspired Po2 is increased to 3 atm (304 kPa) in a hyperbaric chamber, the amount of dissolved oxygen is sufficient to meet normal metabolic demands even in the absence of hemoglobin (Table 15-1).

Oxygen Deprivation

Classically, there are five causes of hypoxemia: low inspired oxygen fraction (Fio2), increased diffusion barrier, hypoventilation, ventilation-perfusion (V/Q ) mismatch, and shunt or venous admixture.

In addition to failure of the respiratory system to oxygenate the blood adequately, a number of other factors can contribute to hypoxia at the tissue level. These may be divided into categories of oxygen delivery and oxygen utilization. Oxygen delivery decreases globally when cardiac output falls or locally when regional blood flow is compromised, such as from a vascular occlusion (e.g., stenosis, thrombosis, or microvascular occlusion) or increased downstream pressure (e.g., compartment syndrome, venous stasis, or venous hypertension). Decreased oxygen-carrying capacity of the blood likewise will reduce oxygen delivery, such as occurs with anemia, carbon monoxide poisoning, or hemoglobinopathy. Finally, hypoxia may occur when transport of oxygen from the capillaries to the tissues is decreased (edema) or utilization of the oxygen by the cells is impaired (cyanide toxicity). Our understanding of some of the cellular responses to hypoxia has been advanced by studies of hypoxia-inducible factors.

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