The order
Danger first, then frequency and reversibility. Say it aloud: oxygen and carbon dioxide, circulation, glucose, paralysis, drug, temperature and sodium, brain.
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Oxygenation and ventilation. Saturation, respiratory rate, chest movement, capnograph. Take a blood gas if the carbon dioxide is a question. These kill in minutes and are already on the monitor.
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Circulation. Blood pressure and rhythm. A brain that is not perfused does not wake.
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Glucose. A meter answers in seconds, and a low reading is treated on the meter rather than on the laboratory.
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Residual paralysis. A quantitative monitor answers in seconds and the patient cannot tell you. The guideline sets a train-of-four ratio of 0.9 or more as recovery and recommends quantitative monitoring over clinical assessment thilen-2023. Sugammadex is dosed by measured depth: 2 mg/kg at the reappearance of the second twitch, 4 mg/kg at one to two post-tetanic counts fda-sugammadex-label-2026.
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Residual drug. Volatile, opioid, benzodiazepine, and the central anticholinergic syndrome. See the reversal agents below.
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Temperature, sodium and the other electrolytes.
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The brain. Pupils, focal signs, imaging. Last because it is rarest and least reversible, not because it does not matter.
The order is expert consensus, not a trial result ellis-2017.
The reversal agents, and their traps
Naloxone. For postoperative opioid depression the label gives increments of 0.1 to 0.2 mg intravenously at two to three minute intervals to the desired degree of reversal. Because the duration of action of some opioids exceeds that of naloxone, whose adult serum half-life ranged from 30 to 81 minutes in one study, the patient must be kept under continued surveillance and repeat doses given as necessary fda-naloxone-label-2023. The small increment widely taught to avoid abrupt reversal is not in that labelling, whose only smaller increments are pediatric fda-naloxone-label-2023. Its one primary source is a 15-patient retrospective emergency department case series, mostly methadone ingestions, starting at 0.04 mg and titrating to a median total of 0.08 mg, in which 2 of 15 went into acute withdrawal kim-2016-naloxone. Wrong setting, wrong population, no control group. Treat it as a practice convention. Abrupt reversal may cause nausea, vomiting, sweating, tachycardia, hypertension, seizures, ventricular arrhythmias, pulmonary edema and cardiac arrest fda-naloxone-label-2023.
If you give naloxone, you have committed to watching the patient for longer than the naloxone lasts.
Flumazenil. 0.2 mg intravenously over 15 seconds, repeated at 60-second intervals up to four further doses, maximum 1 mg. Re-sedation occurred in 3% to 9% in conscious-sedation studies and the terminal half-life is 40 to 80 minutes fda-flumazenil-label-2025. The boxed warning: seizures are most frequent in patients on benzodiazepines for long-term sedation, or in overdose with signs of serious cyclic antidepressant overdose fda-flumazenil-label-2025. Ask what the patient takes at home before you give it.
Physostigmine, for central anticholinergic syndrome, once the commoner causes are excluded. In a recovery-room study it was diagnosed in 18 of 962 patients (1.9%) after prolonged anesthetic or relaxant effect, respiratory depression and metabolic disorder were excluded; all woke after physostigmine and six relapsed and needed a second dose link-1997.
Two physostigmine labels are current in the United States and they do not agree, so know which product you are holding. The approved one names this exact indication, listing central anticholinergic syndrome, delayed postoperative awakening and shivering, and doses by weight: 0.04 mg/kg injected slowly at about 1 mg/min, a maximum single dose of 2 mg, and a repeat after 5 to 20 min at the earliest fda-physostigmine-anticholium-label-2023. The other is marked an unapproved drug and its label carries the statement that it has not been found by the FDA to be safe and effective; its dose is 0.5 to 1.0 mg intramuscularly or intravenously at no more than 1 mg per minute fda-physostigmine-akorn-label-2022. This card used to give 0.5 to 2 mg, which straddled the two and matched the approved label at neither end.
Give it slowly whichever product you have. Both labels warn that rapid administration causes bradycardia, hypersalivation and convulsions, and both keep atropine at hand as the antidote fda-physostigmine-anticholium-label-2023 fda-physostigmine-akorn-label-2022.
Do not
Do not skip to the brain. Do not stop before it either.
Sources
[[fda-naloxone-label-2023]] advisory 2023 n: NA open
Naloxone Hydrochloride Injection, USP [prescribing information]. Hospira, Inc. Revised 07/2023. DailyMed set ID 8535cc84-ad4a-4d67-8480-fb5a2e3406f8.
FDA label. Dosage and Administration: 'Since the duration of action of some opioids may exceed that of naloxone, the patient should be kept under continued surveillance. Repeated doses of naloxone should be administered, as necessary.' Pharmacokinetics: 'the serum half-life in adults ranged from 30 to 81 minutes (mean 64 +/- 12 minutes).' Postoperative opioid depression: 'increments of 0.1 to 0.2 mg intravenously at two to three minute intervals to the desired degree of reversal.' Precautions: abrupt reversal may cause nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest.
[[kim-2016-naloxone]] case series 2016 n: 15 paywalled
Kim HK, Nelson LS. Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series. J Med Toxicol. 2016;12(1):107-110.
THE ONLY PRIMARY SOURCE FOUND FOR A 0.04 mg ADULT NALOXONE INCREMENT, AND IT DOES NOT SUPPORT THE CLAIM AS THE CARD WORDS IT. Retrospective case series, medical-record review, no control group. Setting was the EMERGENCY DEPARTMENT via medical toxicology consultation, not the PACU. 15 patients, of whom 12 had ingested methadone 30-180 mg. Starting dose 0.04 mg IV, titrated; median total 0.08 mg, range 0.04-0.12 mg. 2 of 15 developed acute opioid withdrawal after the 0.08 mg dose. Conclusion, VERBATIM: 'ED patients with moderate to severe opioid-induced ventilatory depression can be reversed using 0.04 mg IV naloxone with appropriate dose titration.' NOTE THE MISMATCH: the card states an increment range of 0.04 to 0.1 mg; this study's observed range runs to 0.12 mg, and the population and setting are both wrong for a PACU page. No society guideline recommending 0.04 mg adult increments was found; the ASA/ASRA neuraxial-opioid respiratory depression guideline gives no naloxone dose at all.
[[fda-flumazenil-label-2025]] advisory 2025 n: NA open
Flumazenil Injection, USP [prescribing information]. Fresenius Kabi USA, LLC. Revised January 2025. DailyMed set ID a72d9fc1-121c-455d-93a9-002378c9968f.
FDA label. Boxed warning (WARNINGS): 'THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF SEIZURES. THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE.' Reversal of sedation/anesthesia (adults): 0.2 mg IV over 15 s; further 0.2 mg at 60-s intervals up to 4 additional doses; maximum cumulative 1 mg. Resedation 3% to 9% in conscious-sedation studies; terminal half-life 40 to 80 minutes.
[[link-1997]] cohort 1997 n: 962 paywalled
Link J, et al. Distinct central anticholinergic syndrome following general anaesthesia. Eur J Anaesthesiol. 1997 Jan;14(1):15-23.
Prospective 2-month recovery-room study: 18/962 (1.9%) developed distinct central anticholinergic syndrome after other causes (prolonged anaesthetic/relaxant action, respiratory depression, metabolic disorder) were excluded; 6/60 women after hysterectomy (P=0.003); untreated somnolence >2 h in 6/18; all woke after physostigmine, 6 relapsed and needed a second (one a third) dose.
[[thilen-2023]] guideline 2023 n: NA open
Thilen SR, Weigel WA, Todd MM, Dutton RP, Lien CA, Grant SA, Szokol JW, Eriksson LI, Yaster M, Grant MD, Agarkar M, Marbella AM, Blanck JF, Domino KB. 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade. Anesthesiology. 2023 Jan 1;138(1):13-41.
TOF ratio >=0.9 is the stated recovery threshold; quantitative monitoring recommended over qualitative/clinical assessment; sugammadex recommended for deep, moderate and shallow rocuronium- or vecuronium-induced block; neostigmine described as a reasonable alternative only from minimal block (TOF ratio 0.4 to <0.9); patients with documented quantitative TOF ratio >=0.9 do not require pharmacologic antagonism
[[fda-sugammadex-label-2026]] advisory 2026 n: NA open
Sugammadex Injection [prescribing information]. Fresenius Kabi USA, LLC. Revised 6/2026. DailyMed set ID 8e685b67-6804-4d97-b43e-0259b3fe231f.
FDA label. Dosing by depth: 2 mg/kg at reappearance of T2; 4 mg/kg at 1-2 post-tetanic counts; 16 mg/kg ~3 min after 1.2 mg/kg rocuronium. Anaphylaxis 0.3% (1/299 healthy volunteers, in the 16 mg/kg group). 'Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration.' Recurrence: lower-than-recommended doses increase risk of recurrence after initial reversal. Hormonal contraceptives: equivalent to a missed dose; additional non-hormonal contraception for 7 days. Waits before re-dosing steroidal NMBA: 5 min (1.2 mg/kg rocuronium), 4 h (0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium), 24 h after 16 mg/kg or in renal impairment.
[[ellis-2017]] consensus statement 2017 n: NA open
Ellis TA 2nd, et al. Delayed Emergence From Anesthesia: A Simulation Case for Anesthesia Learners. MedEdPORTAL. 2017 Sep 18;13:10628.
Educational simulation case (not a study): lists causes of delayed emergence as residual anesthetics, pharmacologic actions, surgical complications, neurologic events, endocrine disturbances, patient factors; emphasises pseudocholinesterase deficiency. Design vocabulary has no term for an educational resource; 'consensus_statement' is a placeholder the director should confirm or the row should be dropped from support and kept as found_via only.
[[fda-physostigmine-anticholium-label-2023]] advisory 2023 n: NA open
ANTICHOLIUM (physostigmine salicylate) injection [prescribing information]. Provepharm Inc. Revised July 2023. DailyMed set ID b90b50e8-c8f1-4f2d-be6e-4d269b8c362c. DailyMed updated 11 November 2025.
THIS IS THE ROW DAY 13 AND THE DELAYED EMERGENCE CARD NEED. This label names the indication explicitly, VERBATIM: 'the treatment of postoperative disorders: Central anticholinergic syndrome (CAS), Delayed postoperative awakening, Shivering'. Adult dose, VERBATIM: 'Slowly inject physostigmine intravenously at a dose of 0.04 mg/kg bodyweight (approx. 1 mg/min), the maximum individual dose is 2 mg.' And: 'In case of insufficient effect, give subsequent injections after 5 to 20 minutes at the earliest.' Administration, VERBATIM: 'Intravenously slowly or as brief infusion in 50 ml physiological saline solution over 10-15 minutes.' Harms, VERBATIM: 'Bradycardia and convulsions, if intravenous administration is too rapid'; 'An overdose of ANTICHOLIUM can cause bradycardia, hypersalivation, vomiting, and generalized tonic-clonic seizures. Patients should be closely monitored by ECG'; and 'Acute cardiac arrest may be possible during treatment with tricyclic antidepressants; therefore, Anticholium should only be considered as an antidote for this indication while the patient has continuous ECG monitoring.' NOTE THE DIVERGENCE FROM THE CARD: the card teaches 0.5 to 2 mg; this label teaches 0.04 mg/kg to a maximum single dose of 2 mg. No label examined contains the word asystole. CAVEAT: some warnings text returned in patient-facing phrasing, so section headings should be re-checked before being cited as Warnings and Precautions.
[[fda-physostigmine-akorn-label-2022]] advisory 2022 n: NA open
Physostigmine Salicylate Injection [prescribing information]. Akorn Operating Company LLC. Revision code PS00N Rev. 10/22. DailyMed set ID a7d04b2c-fe34-480d-8f7c-7cbcf447a70b. DailyMed updated 13 September 2022. Marketing category: unapproved drug other.
SECOND PHYSOSTIGMINE LABEL, AND IT IS AN UNAPPROVED PRODUCT. The DailyMed page carries the FDA disclaimer VERBATIM: 'This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA.' Indication, VERBATIM: 'To reverse the effect upon the central nervous system, caused by clinical or toxic dosages of drugs capable of producing the anticholinergic syndrome.' Dose as printed: 'Past Anesthesia Care: 0.5 to 1.0 mg intramuscularly or intravenously. INTRAVENOUS ADMINISTRATION SHOULD BE AT A SLOW CONTROLLED RATE OF NO MORE THAN 1 MG PER MINUTE. Dosage may be repeated at intervals of 10 to 30 minutes if desired patient response is not obtained.' The words 'Past Anesthesia Care' are as returned and are probably a typographical error for 'Post Anesthesia Care'; VERIFY THE WORD BEFORE QUOTING. Warnings, VERBATIM: 'Rapid administration can cause bradycardia, hypersalivation leading to respiratory difficulties and possible convulsions.' Precautions, VERBATIM: 'Because of the possibility of hypersensitivity in an occasional patient, atropine sulfate injection should always be at hand since it is an antagonist and antidote for physostigmine.' The 0.5 to 1.0 mg figure the card teaches matches THIS label, which is the unapproved one, not the approved Anticholium label. The director should decide which to cite, and say which.