Droperidol + fentanyl

Droperidol-Fentanyl Butyrophenon /r-opioid agonist Neuroleptanalgesia... 

Eight out of 42 patients taking unnamed beta blockers given atracurium developed bradycardia (less than 50 bpm) and hypotension (systolic pressure less than 80 mniHg). Most of them had been premedicated with diazepam, induced with methohexital, and maintained with droperidol, fentanyl and nitrous oxide/oxygen. A further 24 showed bradycardia, associated with hypotension on 9 oeeasions. All responded promptly to 300 to 600 micrograms of intravenous atropine. ... 

Neuroleptic analgesia is so called because the combination of a major tranquilizer, a neuroleptic dmg, and a potent opiate produces an anesthetic state characterized by sedation, apathy, and mental detachment (see Psychopharmacological agents) (152). Iimovar [8067-59-2] a combination of droperidol [648-72-2], C22H22FN2O2, (19) and fentanyl (9) citrate, is used for procedures that do not require muscle relaxation. However, the onset of action is slow. 

The neuroleptic droperidol possesses antipsychotic, sedative, and antishock action. It potentiates the action of drugs for narcosis. In psychiatric practice, droperidol is used for psy-chomotor excitement and hallucinations. The principal use of this drug lies in anesthesiology for neuroleptanalgesia in combination with fentanyl. It is used in premedication as well as in surgical operations and post-operational circumstances. Synonyms of this drug are talam-onal, droleptan, leptofen, innovar, and others. 

Fentanyl is 80 to 100 times as potent as morphine. Sufentanil (Sufenta) is 500- to 1,000-fold more potent than morphine, while alfentanil (Alfenta) is approximately 20 times more potent than morphine. Their onset of action is usually less than 20 minutes after administration. Dosage is determined by the lean body mass of the patient, since the drugs are lipophilic and tend to get trapped in body fat, which acts as a reservoir, prolonging their half-life. In addition, redistribution of the drugs from the brain to fat stores leads to a rapid offset of action. Droperidol, a neuroleptic agent, is generally administered in combination with fentanyl for IV anesthesia. 

Perhaps the most successful modification of the 4-phenylpiperidine derivatives of morphine is the 4-anilino compounds, such as fentanyl (3.15). This dmg is 50-100 times more active than morphine, owing mainly to its excellent transport across the blood-brain barrier and into the CNS as a result of its high lipophilicity. Spectacular activities ( 5000-6000 times that of morphine) have also been achieved by introducing ether or keto substituents (sufentanil), as in the meperidine or ketobemidone series. Fentanyl derivatives are very fast acting and of short duration. They are used in neuroleptanalgesia in surgery, in combination with neuroleptics or major tranquilizers like droperidol. 

The fixed dose combination of fentanyl (0.05 mg) and droperidol (2.5 mg/ml), 4 to 6 ml is diluted in glucose solution and infused IV over 10 minutes. 

Until quite recently, droperidol was used in combination with fentanyl to induce a state of anaesthesia which became known as neuroleptanalgesia... 

Phenothiazines with shorter side chains have considerable H -receptor-blocking action and have been used for relief of pruritus or, in the case of promethazine, as preoperative sedatives. The butyrophenone droperidol is used in combination with an opioid, fentanyl, in neuroleptanesthesia. The use of these drugs in anesthesia practice is described in Chapter 25. 

Droperidol produces a state of decreased anxiety and attention to surroundings. Combined with the opiod fentanyl, it can be used to induce an analgesic state. 

Analgesic efficacy and clinical use Fentanyl (Clotz and Nahata, 1991) is a potent analgesic and anesthetic compound. It is used for the treatment of severe acute and chronic pain, as a pre-medication or adjunct to anesthesia and as a primary anesthetic for the induction or maintenance of anesthesia. In combinations with neuroleptics e.g. droperidole, it induces a pain free and calm state known as neuroleptanalgesia (Foldes, 1973). In this condition, surgery can be performed in an awake patient, who is able to cooperate with the surgeon. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

The combination of droperidol and fentanyl is a fixed ratio preparation called innovar. Since droperidol is a neuroleptic substance, innovar is said to produce neurolept analgesia if combined with a more potent anesthetic, innovar produces neuroleptic anesthesia. A neuroleptic has adrenergic blocking as well as sedative, antiemetic, and anticonvulsant properties. Since innovar can cause extrapyramidal muscle movements, it is contraindicated in Parkinson s patients. 

Fentanyl [FEN ta nil], which is chemically related to meperidine, has 80 times the analgesic potency of morphine, and is used in anesthesia. It has a rapid onset and short duration of action (15 to 30 minutes). When combined with droperidol (see p.117) it produces a neurolept anesthesia. Sufentanil [soo FEN ta nil], a related drug, is even more potent than fentanyl. 

An exception to the relatively safe use of high-potency agents has been noted in the combination of droperidol with the narcotic fentanyl, which can cause marked hypotension (27). 

The addition of droperidol 2.5 mg to fentanyl 0.4 mg in 40 ml of 0.125% bupivacaine lowered the incidence of postoperative nausea and vomiting compared with a solution without droperidol or with butorphanol added instead in patients undergoing anorectal surgery in a prospective randomized, single-blind study (28). 

Kotake Y, Matsumoto M, Ai K, Morisaki H, Takeda J. Additional droperidol, not butorphanol, augments epidural fentanyl analgesia following anorectal surgery. J Clin Anesth 2000 12(1) 9-13. 

Burduk P, Guzik P, Piechocka M, Bronisz M, Rozek A, Jazdon M, Jordan MR. Comparison of fentanyl and droperidol mixture (neuroleptanalgesia II) with morphine on clinical outcomes in unstable angina patients. Cardiovasc Drugs Ther 2000 14(3) 259-69. 

---