Month: February 2020

Aging is a process related to several biological changes that may influence the anesthesia experience. In old age, there is a decrease in nervous system tissue mass, particularly a decline in grey matter brain volume, neuronal density, and concentration of neurotransmitters [1, 2]. These changes mean that older patients, particularly those above 65 years old, are more sensitive to anesthesia and may have more complications following anesthesia than younger patients [1]. The increased sensitivity to anesthesia in elderly patients means that anesthesiologists may be able to use less anesthesia to achieve proper sedation in older patients compared to younger ones [1].

Depending on anesthesia type, the amount of drug needed for the desired effect changes. For inhalation anesthesia, the amount of drug needed decreases by about 6% each decade of life [1]. For certain opioids, such as fentanyl, the potency of the drug increases almost two-fold in an elderly patient, making the correct dosage of pre- and post-surgery pain medicine much lower compared to that needed in younger patients [1]. Another result of aging on the anesthesia experience is a greater susceptibility to experiencing post-operative cognitive dysfunction and delirium.

Post-operative cognitive dysfunction (POCD) is defined as an impairment in cognitive abilities, such as memory, perception, and attention, following surgery [3]. In patients above 60 years old, the risk of developing POCD a week after major surgery is 25% [4]. Three months post-surgery, POCD incidence in patients above 60 years old is about 10% [4]. Furthermore, the risk of developing POCD is nearly three times higher in patients above 80 years old compared to middle-aged patients [5]. However, anesthesia type may relate to this risk of development. Silvert et al. (2014) found that the incidence of POCD in elderly patients 1 week after surgery with general anesthesia was 4.1% compared to 11.9% after surgery with regional anesthesia and without sedation or post-operative opioids [6]. Three months post-surgery, the incidence of POCD was 6.8% in the group that received general anesthesia and 19.6% in the group that received regional anesthesia [6]. Nonetheless, the authors did not conclude that general anesthesia lowers the incidence of POCD, instead they argued that the surgery type may have more to do with the development of POCD in the elderly patients than the anesthesia type [6].

Post-operative delirium (POD), in contrast, refers to a state following surgery where the patient has “reduced awareness of the environment and a disturbance in attention,” typically 1-3 days post-surgery [3]. The incidence of POD in elderly patients ranges between 5-15% [3]. One randomized double-blind study found that elderly patients (>65 years old) who received deep sedation had a greater incidence of POD than elderly patients who received light sedation [2]. In addition to these increased risks of POCD and POD, elderly patients may also take a longer amount of time to recover from anesthesia compared to their younger counterparts [1, 2]. Despite evidence of these negative post-operative effects, there is also some evidence to suggest that elderly patients may be almost four times less likely to experience any adverse event during surgery or develop post-operative nausea and vomiting and drowsiness than younger patients [7].

Overall, there is no conclusive evidence that anesthesia should not be used in elderly patients and most patients recover to their peers’ cognitive ability shortly after surgery. Instead, anesthesiologists should carefully monitor the amount of anesthetic given to limit the risk of POCD and POD in elderly patients who are highly sensitive to anesthesia.

References:

1. Kanonidou, Z. & Karystianou, G. (2007). Anesthesia for the Elderly. Hippokratia, 11(4), 175-177.
2. Strøm, C., Rasmussen, L.S., & Sieber, F.E. (2014). Should general anesthesia be avoided in the elderly? Anaesthesia, 69(Supp1), 35-44. doi:10.1111/anae.12493.
3. Deiner, S. & Silverstein, J.H. (2009). Postoperative delirium and cognitive dysfunction. BJA: British Journal of Anaesthesia, 103(Supp1), i41-i46. doi: 10.1093/bja/aep291
4. Moller, J.T. et al. (1998). Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. Lancet, 351(9106), 857-61. doi: 10.1016/s0140-6736(97)07382-0
5. Johnson T., et al. (2002) Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology, 96, 1351–7
6. Silbert BS, Evered LA, Scott DA. (2014). Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy. Br J Anaesth; 113(5), 784-791. doi: 10.1093/bja/aeu163
7. Chung, F., Mezei, G., & Tong, D. (1999). Adverse events in ambulatory surgery. A comparison between elderly and younger patients. Canadian Journal of Anaesthesia, 46, 309-321. doi: 10.1007/BF03013221

Sufentanil is a potent synthetic opioid drug that is a derivative of fentanyl.¹ Sufentanil was developed in the early 1970s as a highly potent version of fentanyl, used for intravenous anesthesia.² Since then, prescription of sufentanil has broadened to include epidural and sublingual forms.³ Sufentanil is commonly sold under the brand names Dsuvia (a sufentanil sublingual tablet) or Sufenta (a sufentanil citrate injection).³ Because of its role in pain management and anesthesia, anesthesiology professionals should be familiar with sufentanil’s biological mechanisms, applications and side effects.

The molecular formula of sufentanil is C₂₂H₃₀N₂O₂S,⁴ though it can also take the salt form of sufentanil citrate, which is C₂₈H₃₈N₂O₉S.⁵ Sufentanil and its salt form exert their actions by binding selectively to m-opioid receptors in the brain and spinal cord.³ As m-opioid receptors are G-protein-coupled receptors, sufentanil’s binding affects the behavior of G-proteins in neurons.³ This leads to biochemical chain of reactions that causes decreased neural signaling and reduced neurotransmitter release, which contribute to sufentanil’s analgesic effects.³ Sufentanil undergoes metabolism by CYP3A4 enzymes in the liver.⁶ Unlike opioids such as morphine or hydromorphone, sufentanil has no active metabolites.⁷ Its inactive metabolites are excreted in urine and feces.⁶ Sufentanil is highly liphophilic, which allows for quick absorption of the drug by bodily tissues and rapid distribution around the body.⁷ It is more lipid soluble than fentanyl and alfentanil, which are other commonly used opioid drugs.⁸ More than 90 percent of sufentanil is protein bound, which is responsible for its small volume of distribution and short duration of action.⁸

Sufentanil has unique uses in anesthesiology due to its more rapid onset of action, quicker distribution and elimination and greater potency than fentanyl.¹ Like other opioids, sufentanil has dose-dependent effects that allow it to be used as an adjunct in anesthesia, in balanced anesthesia and as a primary anesthetic agent.³ Depending on the purpose, sufentanil can be administered intravenously, epidurally, sublingually or even intranasally.^3,9 Intranasal sufentanil can be used during the preoperative period to induce sedation.⁹ Intravenous sufentanil can be provided during surgery in high anesthetic doses or in lower doses as a supplement to other anesthetics.¹ Additionally, epidural sufentanil serves as an analgesic during labor and vaginal delivery.^1,3 In its sublingual form, sufentanil provides acute pain management in adults,³ particularly during the postoperative period.⁶ Sufentanil and other fentanyl analogs have advantages over morphine, meperidine and inhalational anesthetics because they produce hypnosis and repress hemodynamic responses to surgery without producing cardiovascular depression.¹⁰ Therefore, sufentanil can be useful for anesthesia in major cardiovascular procedures and analgesia for situations requiring pain management.³

Because sufentanil has no active metabolites, it has a decreased risk of unwanted side effects when compared to other opioid drugs.^6,7 However, sufentanil can cause nausea, vomiting, itching and urinary retention,¹¹ as well as reduced gastrointestinal motility.¹² Other side effects include depression of the cough reflex, hypotension and slow heart rate.³ Its high protein binding leads to slower elimination from the body than other opioids, which makes it possible for plasma drug concentrations to increase even after discontinuation.¹³ Similar to other opioids, overdose of sufentanil can cause respiratory depression.¹³ Furthermore, sufentanil has addictive properties, especially in its injected form.⁴

Sufentanil is a synthetic opioid that is more potent than its analog, fentanyl. Sufentanil acts on opioid receptors in the brain to reduce neuronal activity and lower the release of neurotransmitters. It has a quicker onset and shorter duration of action than fentanyl, and can be used for analgesia or anesthesia. Sufentanil can be administered intranasally, intravenously, epidurally or sublingually. Like other opioid drugs, sufentanil has adverse effects such as nausea, vomiting, itching, hypotension, slow heart rate and even respiratory depression or death. Sufentanil should be prescribed sparingly given its abuse potential.

1.         Monk JP, Beresford R, Ward A. Sufentanil. A review of its pharmacological properties and therapeutic use. Drugs. 1988;36(3):286–313.

2.         Niemegeers CJ, Schellekens KH, Van Bever WF, Janssen PA. Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs. Arzneimittel-Forschung. 1976;26(8):1551–1556.

3.         Sufentanil. DrugBank February 10, 2020; https://www.drugbank.ca/drugs/DB00708.

4.         Sufentanil. PubChem Database. Web: National Center for Biotechnology Information; 2020.

5.         Sufentanil citrate. PubChem Database. Web: National Center for Biotechnology Information; 2020.

6.         Sindt JE, Jenkinson RH. 18—Nonintravenous Opioids. In: Hemmings HC, Egan TD, eds. Pharmacology and Physiology for Anesthesia (Second Edition). Philadelphia: Elsevier; 2019:354–368.

7.         Sufentanil. AcelRx Pharmaceuticals 2013; https://www.acelrx.com/technology/sufentanil.html.

8.         Koyyalagunta D. Chapter 113—Opioid Analgesics. In: Waldman SD, Bloch JI, eds. Pain Management. Philadelphia: W.B. Saunders; 2007:939–964.

9.         Chapter 9—Sublingual, Transdermal, and Intranasal Sedation. In: Malamed SF, ed. Sedation (Sixth Edition): Mosby; 2018:125–133.

10.       Rosow CE. Sufentanil citrate: A new opioid analgesic for use in anesthesia. Pharmacotherapy. 1984;4(1):11–19.

11.       Krames ES, Harb M. Chapter 33—The Rational Use of Intrathecal Opioid Analgesics. In: Krames ES, Peckham PH, Rezai AR, eds. Neuromodulation. San Diego: Academic Press; 2009:441–455.

12.       National Cancer Institute. Sufentanil citrate. In: National Institutes of Health, ed. NCI Drug Dictionary 2020.

13.       Anderson BJ, Lerman J, Coté CJ. 7—Pharmacokinetics and Pharmacology of Drugs Used in Children. In: Coté CJ, Lerman J, Anderson BJ, eds. A Practice of Anesthesia for Infants and Children (Sixth Edition). Philadelphia: Elsevier; 2019:100–176.e145.

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Welcome to WordPress. This is your first post. Edit or delete it, then start writing! Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry’s standard dummy text ever since the 1500s, when an unknown printer took a galley of type and scrambled it to make a type specimen book. It has survived not only five centuries, but also the leap into electronic typesetting, remaining essentially unchanged. It was popularised in the 1960s with the release of Letraset sheets containing Lorem Ipsum passages, and more recently with desktop publishing software like Aldus PageMaker including versions of Lorem Ipsum.

Welcome to WordPress. This is your first post. Edit or delete it, then start writing! Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry’s standard dummy text ever since the 1500s, when an unknown printer took a galley of type and scrambled it to make a type specimen book. It has survived not only five centuries, but also the leap into electronic typesetting, remaining essentially unchanged. It was popularised in the 1960s with the release of Letraset sheets containing Lorem Ipsum passages, and more recently with desktop publishing software like Aldus PageMaker including versions of Lorem Ipsum.
Welcome to WordPress. This is your first post. Edit or delete it, then start writing! Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry’s standard dummy text ever since the 1500s, when an unknown printer took a galley of type and scrambled it to make a type specimen book. It has survived not only five centuries, but also the leap into electronic typesetting, remaining essentially unchanged. It was popularised in the 1960s with the release of Letraset sheets containing Lorem Ipsum passages, and more recently with desktop publishing software like Aldus PageMaker including versions of Lorem Ipsum.