Editorial
Tríada de Friedberg, un camino hacia la anestesia libre de opioides y mejores resultados
Friedberg’s Triad, a pathway to opioid free anesthesia (OFA) and better outcomes
2021 / DOI: 10.20986/mpj.2021.1004/2021
Barry L. Friedberg1
1UC Irvine Health (Corona del Mar)
Recepción: 1 junio 2021
Aceptación: 1 junio 2021
Publicación: 20 julio 2021
Resumen
La tríada de Friedberg (es decir: monitorizar la función cerebral, adelantarse al dolor, abstenerse de los fármacos emetizantes) se conceptualizó como una vía hacia la anestesia libre de opioides (OFA, por sus siglas en inglés) y poder obtener los mejores resultados. El retraso del despertar, el dolor postoperatorio y las náuseas y vómitos postoperatorios (VPO) son resultados que deben prevenirse. El retraso del despertar es a menudo secundario a la sobremedicación, la consecuencia natural de la falta de monitorización directa del efecto anestésico en el órgano objetivo, el cerebro. La medición directa revela una variación interindividual de 100 veces en los requisitos de propofol para lograr el mismo nivel de sedación. La titulación incremental del propofol a BIS <75 con EMG de la línea de fondo fija la etapa para la pre-estimulación sin alucinaciones en 2-5 minutos (es decir, incisión de la piel o inyecciones anestésicas locales múltiples) con la administración de 50 mg de ketamina independientemente del peso corporal o de la edad. El dolor postoperatorio es una consecuencia de la saturación fallida del receptor NMDA preestimulación, lo que conduce a la nocicepción intraoperatoria.
Con la ventilación espontánea, los picos de EMG en tiempo real son una señal de tendencia BISTM secundaria a la excitación incipiente. La excitación precede a la nocicepción. La prevención del despertar con propofol adicional previene el despertar y el dolor intraoperatorios. La ausencia de punto de EMG con el estímulo es evidencia objetiva y reproducible de la presunción de la saturación del receptor de NMDA y del comienzo de la analgesia, preventiva del opiáceo. La anestesia general profunda no previene la nocicepción.
Las nauseas y vómitos postoperatorios (NVPO) son un efecto adverso bien reconocido de los opioides. La OFA elimina las náuseas y los vómitos postoperatorios incluso sin la administración de antieméticos en una población de alto riesgo definida por el test de Apfel. Los opioides no previenen el dolor postoperatorio y aumentan las náuseas y vómitos postoperatorios.
Puede haber muchas razones para que los anestesiólogos no elijan la OFA, entre las cuales no es menor el miedo a las alucinaciones de la ketamina, el miedo al dolor postoperatorio o la crítica de los colegas.
Este editorial puede ayudar a superar los dos primeros miedos y la resistencia al cambio. En lugares de todo el mundo, los pacientes operados bajo la técnica OFA se han regocijado, especialmente aquellos que han experimentado previamente NVPO o dolor. Puedo entender la renuencia a cambiar, pero no la renuencia a hacerlo mejor para los pacientes.
Palabras clave: Tríada de Friedberg, opioides
Abstract
Friedberg’s Triad (i.e. Measure the brain, Preempt the pain, Emetic drugs abstain) was conceptualized as a pathway to opioid free anesthesia (OFA) and better outcomes. Prolonged emergence, postoperative pain and postoperative nausea and vomiting (PONV) are outcomes to be prevented. Prolonged emergence is often secondary to overmedication, the natural consequence to failure to directly measure anesthetic effect on the target organ, the brain. Direct measurement reveals a 100-fold inter-individual variation in propofol requirements to achieve the same numerical sedation level. Incremental propofol titration to BIS <75 with baseline EMG sets the stage for hallucination-free, 2-5 minutes pre-stimulation (i.e. skin incision or multiple local anesthetic injections) 50 mg ketamine independent of body weight or age. Postoperative pain is a function of failed pre-stimulation NMDA receptor saturation leading to intra-operative nociception (pain). With spontaneous ventilation, real time EMG spikes as a secondary BISTM trend signal incipient arousal. Arousal precedes nociception. Arousal prevention with additional propofol prevents intra-operative arousal and nociception. Absence of EMG spike with stimulation is objective, reproducible prima facie evidence of NMDA receptor saturation and the beginning of opioid free, preemptive analgesia. Deep general anesthesia does not prevent nociception.
PONV is a well-recognized opioid-related adverse drug effect. OFA eliminates PONV even without antiemetic administration in an Apfel-defined high risk population. Opioids do not prevent postoperative pain but increase PONV.
There may be many reasons for anesthesiologists not electing to pursue OFA, not the least of which is fear of ketamine hallucinations, fear of postop pain or criticism of colleagues. This editorial may help overcome the first two fears and resistance to change. In places around the world, OFA patients have rejoiced, especially those who’ve previously experienced PONV or pain. I can understand the reluctance to change but not the reluctance to do better for patients.
Keywords: Friedberg’s Triad, opioid
Artículo Completo

Friedberg’s Triad is 1) Measure the brain, 2) Preempt the pain, 3) Emetic drugs abstain (1) (Figure 1).

Why measure the brain? “If you cannot measure it, you cannot improve it”: Lord Kelvin

Why preempt the pain? “An ounce of prevention is worth a pound of cure”: Ben Franklin.

Why abstain from emetic drugs? “As long as emetogenic drugs are part of the anesthetic regimen, the use of anti-emetics is of limited utility”: Christian Apfel.

No anesthesiologist would administer a blood pressure (BP) medication and fail to measure the BP response. Yet, in the 21st century, many continue to administer brain medications (i.e. anesthetics) and fail to directly measure the brain response. The 1996 Food and Drug Administration (FDA) approval of the first modern processed EEG monitor, the bispectral (BIS) indexTM, paved the way for practical direct measurement of cortical response to anesthetic agents like propofol and halogenated inhalational agents. There are other processed EEG monitors (i.e. SedLineTM and Entropy TM), but no publications assert superiority to BIS. My 20-year processed EEG monitoring experience was with the BIS.

Much literature has been devoted to BIS monitoring and awareness with recall. No deaths have been reported from awareness with recall. However, one American death occurs every day, independent of comorbidities, from anesthesia over medication, the natural consequence of failure to directly measure cortical response to anesthesia (2).

The limitation of processed EEG monitoring is the time required to process the response. BIS values are delayed 15-30 seconds from real time and may appear like a short interval. However, the outcome of such a delay leaves the anesthesiologist ‘catching up’ to patient changes in hypnosis levels. This time delay deficiency can be remedied by selecting real time EMG as the secondary BIS trend in the free-standing model (Figure 2). EMG spikes signal incipient arousal, an indication of what is about to happen to the patients’ hypnosis level. Arousal precedes nociception. Think hand touching a hot stove. Withdrawal precedes ‘ouch,’ not the other way around. Giving more propofol with alacrity to drive an EMG spike back to baseline prevents arousal. No arousal, no nociception!

Incremental, not bolus, propofol induction/maintenance with processed EEG monitoring allowed most patients to achieve moderate to deep sedation levels of 60 < BIS < 75 with baseline EMG at 25-50 mcg·kg-1·min-1. A few extremely sensitive, otherwise healthy patients required as little as 2 mcg·kg-1·min-1 while a few extremely resistant patients required as much as 200 mcg·kg-1·min-1 to achieve identical levels of sedation. Directly measuring effect allowed my patients to expose a 100-fold variation in propofol requirements to achieve numerically measured sedation levels. Providing a stable CNS propofol level is important to ketamine hallucination prevention as well as providing a statistically significant 30 % reduction in propofol (3).

Earlier attempts at pain preemption involved administering local analgesia after the induction of general anesthesia (GA) proved unsuccessful. GA does not block, much less saturate, critical subcortical NMDA receptors. In other words, despite GA, the brain is capable of receiving nociceptive stimulation. The so-called dissociative ketamine effect is immobility to noxious stimulation; i.e. multiple subcutaneous local anesthetic injections in cosmetic surgery or skin incision in medically indicated surgery.

Ketamine is our most unique pharmacologic agent. After achieving a stable CNS propofol level, the same 50 mg ketamine dose administered 2-5 minutes pre-stimulation, in more than 6,000 patients over 26 years, produced immobility in patients weighing between 30-146 kg and in ages between 7-94. I do not believe the effective NMDA saturating ketamine dose varies with body weight or age.

Violation of the barrier between the outside world of danger and the inner, protected world of self (i.e. the integument) is constant independent of cosmetic or medically indicated surgery (Figure 3). Once sedated, patients cannot differentiate between the therapeutic intent of a surgeon’s scalpel and the malevolent intent of a mugger’s knife. Prima facie evidence of NMDA receptor saturation is the absence of EMG spikes with noxious stimulation (4). The limitation of using EMG spikes is limited with neuromuscular blocking (NMB) agents. Increasing numbers of patients are receiving ultrasound guided regional anesthesia (UGRA) for major surgeries wherein NMB are not required. BIS/EMG trending will work as well for these surgeries as it has for mine.

In 1999, Macario et al published two scientifically validated surveys of anesthesiologists’ and patients’ attitudes regarding what anesthesia outcome to avoid was most desired (5,6). Unsurprisingly, anesthesiologists chose pain. Paradoxically, patients chose postoperative nausea and vomiting (PONV). When patients sign a surgical consent, some degree of postoperative discomfort is an expectation. PONV, in particular, repeated emesis characteristic of opioid side effects, is most definitely not a patient expectation.

Why then do anesthesiologists pay so little attention to patients’ number one outcome to avoid? Pain is a phenomenon we believe we are preventing in the OR whereas emesis is something that happens out of sight in recovery. Compounding the conundrum is our century-long belief opioids are effective in preventing pain during as well as after surgery. Lichtner et al published nociceptive activation persists even during deep general anesthesia (7). Frauenknecht et al meta-analysis of
23 studies in 1304 patients showed opioid-inclusive anesthesia not only failed to prevent postoperative pain but also increased PONV (8).

These two publications were compatible with my 20-year paradigm of processed EEG monitored propofol then pre-stimulation 50 mg ketamine then local anesthesia (9). What outcomes support my paradigm? Twenty-years in more than 4,000 opioid free outpatients produced not a single hospital admission for either pain or PONV. There were no opioid addicts and no opioid overdose deaths.

There may be many reasons for anesthesiologists not electing to pursue OFA, not the least of which is fear of ketamine hallucinations, postop pain or colleagues’ criticism. My prayers are for this editorial to overcome the first two reasons. In places around the world, OFA patients have rejoiced, especially those who’ve previously experienced PONV or pain. I can understand the reluctance to change but not the reluctance to do better for patients. Carpe diem, patiens aegroti sumus!

Most of my papers can be found on open access Researchgate. My YouTube channel contains many of my opioid free lectures including my most recent webinar, shorturl.at/rEIJ8.

Disclaimer

Neither I nor my self-funded nonprofit Goldilocks Anesthesia Foundation have any financial interests to disclose.

 

references

1. Friedberg BL. Can Friedberg’s Triad solve persistent anesthesia problems? Over-Medication, Pain Management, Postoperative Nausea and Vomiting. Plast Reconstr Surg Global Open. 2017;510):e1527-1734. DOI: 10.1046/j.1524-4725.2000.00074.x.

2. Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of Anesthesia-related Mortality in the United States, 1999-2005. Anesthesiol. 2009;110(4):759-65. doi: 10.1097/aln.0b013e31819b5bdc.

3. Friedberg BL, Sigl JC. Clonidine premedication decreases propofol consumption during bispectral (BIS) index monitored propofol-ketamine technique for office-based surgery. Dermatol Surg. 2000;26(9):848-52. DOI: 10.1046/j.1524-4725.2000.00074.x.

4. Friedberg BL. Opioid free anesthesia with BIS/EMG monitored propofol ketamine (Anestesia libre de opioides con propofol-ketamina monitorizada mediante BIS/EMG). Rev Esp Anestesiol. 2018;65(5):243-5. DOI: 10.1016/j.redar.2017.11.

5. Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg. 1999;88(5):1085. DOI: 10.1097/00000539-199905000-00023.

6. Macario A, Weinger M, Carney S, Kim A. Which clinical anaesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999;89(3):652-8 DOI: 10.1097/00000539-199909000-00022.

7. Lichtner G, Auksztulewicz R, Velten H, Mavrodis D, Scheel M, Blankenburg F, et al. Nociceptive activation in the spinal cord & brain persists DURING deep general anesthesia. Br J Anaesth. 2018;121(1):291-302. DOI: 10.1016/j.bja.2018.03.031.

8. Frauenknecht J Kirkham KR, Jacot-Guillarmod A, Albrecht E. Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia, a systematic review and meta-analysis. Anaesthesia. 2019;74(5):651-62. DOI: 10.1111/anae.14582.

9. Friedberg BL. Postoperative pain, nausea and vomiting (PONV) need not continue to plague our patients – 25 years of propofol ketamine (PK) considered. Anaesth, Pain & Intens Care (APIC) 2017;21(4):399-401. DOI: 10.1097/GOX.0000000000001527.

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Bibliografía
1. 1. Friedberg BL. Can Friedberg’s Triad solve persistent anesthesia problems? Over-Medication, Pain Management, Postoperative Nausea and Vomiting. Plast Reconstr Surg Global Open. 2017;510):e1527-1734. DOI: 10.1046/j.1524-4725.2000.00074.x.
2. 2. Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of Anesthesia-related Mortality in the United States, 1999-2005. Anesthesiol. 2009;110(4):759-65. doi: 10.1097/aln.0b013e31819b5bdc.
3. 3. Friedberg BL, Sigl JC. Clonidine premedication decreases propofol consumption during bispectral (BIS) index monitored propofol-ketamine technique for office-based surgery. Dermatol Surg. 2000;26(9):848-52. DOI: 10.1046/j.1524-4725.2000.00074.x.
4. 4. Friedberg BL. Opioid free anesthesia with BIS/EMG monitored propofol ketamine (Anestesia libre de opioides con propofol-ketamina monitorizada mediante BIS/EMG). Rev Esp Anestesiol. 2018;65(5):243-5. DOI: 10.1016/j.redar.2017.11.
5. 5. Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg. 1999;88(5):1085. DOI: 10.1097/00000539-199905000-00023.
6. 6. Macario A, Weinger M, Carney S, Kim A. Which clinical anaesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999;89(3):652-8 DOI: 10.1097/00000539-199909000-00022.
7. 7. Lichtner G, Auksztulewicz R, Velten H, Mavrodis D, Scheel M, Blankenburg F, et al. Nociceptive activation in the spinal cord & brain persists DURING deep general anesthesia. Br J Anaesth. 2018;121(1):291-302. DOI: 10.1016/j.bja.2018.03.031.
8. 8. Frauenknecht J Kirkham KR, Jacot-Guillarmod A, Albrecht E. Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia, a systematic review and meta-analysis. Anaesthesia. 2019;74(5):651-62. DOI: 10.1111/anae.14582.
9. 9. Friedberg BL. Postoperative pain, nausea and vomiting (PONV) need not continue to plague our patients – 25 years of propofol ketamine (PK) considered. Anaesth, Pain & Intens Care (APIC) 2017;21(4):399-401. DOI: 10.1097/GOX.0000000000001527.
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