The Complex Interplay of General Anesthesia and Sensory Processing: Insights from Propofol Studies


General anesthesia is a medical procedure that plays a pivotal role in various surgical and medical interventions, with nearly 60,000 procedures taking place every day in the United States alone (Brown et al., 2010).

A cornerstone of general anesthesia is achieving unconsciousness, where the patient remains unaware of their surroundings and the ongoing medical procedure (Brown et al., 2010).

However, there exists a rare but disconcerting occurrence known as intraoperative awareness, which happens when the goal of unconsciousness is not achieved (Ghoneim, 2000).

Patients who experience this phenomenon report severe trauma (Kotsovolis & Komninos, 2009), emphasizing the importance of understanding the mechanisms that underlie general anesthesia, particularly its impact on sensory processing.

Historically, research in the field of anesthesia has predominantly focused on the physiological changes brought about by anesthetics. While this knowledge has been instrumental in advancing the safety and efficacy of anesthesia, it often overlooks the critical aspect of how these drugs affect the processing of sensory inputs. To bridge this gap in our understanding, the current study aimed to investigate the impact of the widely used anesthetic, propofol, on the processing of sensory information.

Propofol administration is the process of delivering propofol, a medication used for anesthesia and sedation, to a patient. Propofol is administered intravenously, meaning that it is injected into a vein.

Propofol administration can be used for a variety of purposes, including:

  • Induction of general anesthesia: Propofol is commonly used to induce general anesthesia, which is a state of unconsciousness that is necessary for many surgical procedures.
  • Maintenance of general anesthesia: Propofol can also be used to maintain general anesthesia once it has been induced.
  • Procedural sedation: Propofol can be used to sedate patients for procedures that are not typically performed under general anesthesia, such as colonoscopies and endoscopies.
  • Monitored anesthesia care (MAC): Propofol can also be used to provide MAC, which is a type of sedation that allows patients to be awake but comfortable during procedures.

Propofol administration can be done by a variety of healthcare professionals, including anesthesiologists, nurses, and other medical technicians. The specific method of administration will vary depending on the purpose of the sedation.

For induction of general anesthesia, propofol is typically administered as a bolus injection. This means that the entire dose of propofol is injected over a short period of time. For maintenance of general anesthesia and procedural sedation, propofol is typically administered as an infusion. This means that propofol is delivered to the patient over a longer period of time, typically through a pump.

Propofol administration is a relatively safe procedure, but there are some potential risks associated with it. These risks include:

  • Hypotension: Propofol can cause a decrease in blood pressure.
  • Respiratory depression: Propofol can cause a decrease in respiratory rate and depth.
  • Apnea: In rare cases, propofol can cause complete cessation of breathing.
  • Adverse effects on the heart: Propofol has been linked to an increased risk of heart arrhythmias in some patients.

It is important to monitor patients closely after propofol administration to identify and manage any potential adverse effects.

Here are some specific examples of how propofol administration is used in different clinical settings:

  • In the operating room: An anesthesiologist may administer propofol to a patient before surgery to induce general anesthesia. The anesthesiologist may then continue to administer propofol throughout the surgery to maintain anesthesia.
  • In the endoscopy suite: A nurse may administer propofol to a patient before an endoscopy to sedate the patient and make the procedure more comfortable.
  • In the intensive care unit: A nurse or other healthcare professional may administer propofol to a patient in the ICU to sedate the patient and provide MAC for procedures such as chest X-rays or catheter insertion.

Propofol administration is a valuable tool for healthcare professionals to help patients undergo a variety of procedures safely and comfortably.

The Complex Nature of Propofol

Propofol, a widely employed anesthetic, has garnered attention due to its unique molecular mechanism of action. It functions as a GABA-agonist, influencing the brain’s inhibitory neurotransmission (Bai et al., 1999; Hemmings et al., 2005, 2019). Although its molecular action is well-understood, there is still a considerable gap in comprehending how propofol operates at the level of functional brain networks (Purdon et al., 2013; Brown et al., 2011; Lewis et al., 2012, 2013).

Electrophysiological studies have shown that propofol induces distinct changes in brain activity. It leads to an overall increase in slow oscillations (0.1-4Hz) in electroencephalogram (EEG) and local field potential (LFP) recordings, while simultaneously causing a broad reduction in spiking activity (Bastos et al., 2021; Redinbaugh et al., 2020; Purdon et al., 2015).

These oscillations create a rhythmic alternation between high and low neural activity states known as “Up” and “Down” states, respectively, with spiking activity tightly coupled to the phase of these oscillations (Lewis et al., 2012; Bastos et al., 2021).

The Implications of Propofol-Induced Changes in Sensory Processing

These changes in neural activity patterns induced by propofol are of paramount interest, as they may disrupt the coordination and synchronization between different regions of the cortex, which is vital for effective communication within the brain (Lewis et al., 2012; Bastos et al., 2021; Redinbaugh et al., 2020; Fries, 2015; Pesaran et al., 2018).

Notably, research has shown that sensory responses weaken in higher cortical areas while being relatively preserved in lower sensory cortex regions under the influence of propofol (Krom et al., 2020; Ishizawa et al., 2016). These findings hint at the possibility that the drug may affect the transmission of sensory information from lower to higher cortical areas.

Investigating the Effects of Propofol on Sensory Processing

To shed light on these complex interactions, the current study examined data collected from non-human primates during a previous investigation on propofol anesthesia (Bastos et al., 2021). The study compared and contrasted cortical responses to auditory and tactile stimulation before and after the loss of consciousness induced by propofol.

The analysis encompassed simultaneous recordings of local field potentials (LFP) and spiking activity from multiple cortical levels, including the sensory cortex (temporal cortex), associative cortex (parietal cortex), and higher-level cortex (frontal cortex). By observing the neural activity at these different levels, the researchers aimed to understand how propofol anesthesia might affect the transmission of sensory information throughout the cortex.

The study’s findings

The results of the study revealed that propofol anesthesia does not significantly impair sensory processing in the sensory cortex, which aligns with previous research (Krom et al., 2020; Ishizawa et al., 2016). However, a notable and significant change was observed when it came to the transmission of these sensory signals to higher-level cortical areas.

The data demonstrated that the influence of propofol disrupts the effective communication and transmission of sensory information from the sensory cortex to higher-level cortex areas. This disruption could potentially explain the decreased sensory responsiveness in the higher cortical regions and provide insight into the neural underpinnings of intraoperative awareness, where patients remain aware during surgery despite being under anesthesia.


The study’s findings shed light on the intricate relationship between the administration of propofol anesthesia and the processing of sensory information in the brain, offering new insights into the neural mechanisms responsible for intraoperative awareness and the overall effects of this widely used anesthetic.

Persistence of Auditory Cortex Responses in Unconscious State

One of the key findings of our study was the persistence of sensory responses in the auditory cortex during the unconscious state induced by propofol. This result is consistent with previous research (Krom et al., 2020; Ishizawa et al., 2016; Supp et al., 2011; Liu et al., 2012; Nourski et al., 2017, 2018) and highlights the remarkable resilience of the sensory cortex to the effects of propofol, even in an unconscious state.

Progressive Loss of Information in Higher Cortical Areas

However, the study also revealed that as sensory information progresses from the auditory cortex to higher-order areas, there is a significant reduction in stimulus-related information. This reduction was particularly striking in the parietal and prefrontal cortex. In prefrontal cortex, stimulus information was nearly absent, indicating a profound disruption in sensory processing and integration.

Disruption of Cortical Communication

The disappearance of stimulus-induced alpha-beta coherence between different cortical areas during the unconscious state suggests a breakdown in the coordination of sensory information across the cortex. This is a critical finding, as it implies that propofol anesthesia may impair the communication between various cortical regions.

This disruption of long-range cortical communication aligns with Dehaene and Changeux’s (2011) hypothesis, which suggests that conscious awareness relies on broadcasting cortical activity across the cortex through long-range projections. Such disruptions in cortical communication may contribute to the loss of consciousness and intraoperative awareness.

The Role of Up and Down States

Our results challenge the notion that Up states during propofol-induced unconsciousness represent brief windows of normal conscious activity within the brain. While Up states were associated with increased spiking in the auditory cortex, these responses were notably reduced compared to the Awake state. In higher-order cortical areas, the spiking responses observed in the Awake state were significantly diminished or entirely absent in the Unconscious state. These findings suggest that Up states represent a unique neurophysiological state, distinct from normal conscious activity.

Potential Mechanisms of Sensory Processing Disruption

There are several hypotheses concerning the mechanisms responsible for the disruption of sensory processing during anesthesia. Our findings, along with others, suggest that the disruption occurs primarily within the cortex, as opposed to the thalamic gating hypothesis, which implies that sensory processing is disrupted at the thalamic relay to primary sensory cortex.

One plausible explanation for our results is the “multiple-hit mechanism,” which posits that numerous small perturbations accumulate along sensory processing pathways (Krom et al., 2020). However, our data suggests a substantial drop-off in information processing between sensory cortex and parietal/frontal cortex.

Future Directions and Clinical Implications

The results of this study have significant implications for the field of anesthesiology, particularly in understanding the mechanisms underlying intraoperative awareness. The neural signatures identified in this study, such as the disruption of inter-areal coherence and the progressive loss of information processing along the cortical hierarchy, may serve as valuable targets for monitoring patients under general anesthesia. This monitoring can help ensure that patients remain in a state of true unconsciousness, preventing the distressing experience of intraoperative awareness.


Understanding the complexities of how general anesthesia affects sensory processing in the brain is a critical step in enhancing patient safety and reducing the risk of intraoperative awareness. The study’s findings, which were based on propofol-induced changes in neural activity, underscore the importance of investigating the entire sensory processing chain, from lower to higher cortical areas.

While much remains to be explored in this intricate field of research, the results of this study offer valuable insights into the neural mechanisms underlying the impact of general anesthesia, particularly propofol, on sensory processing. Further studies and continued exploration of these mechanisms will ultimately contribute to improving the safety and efficacy of anesthetic procedures, ensuring that patients are genuinely unconscious and unaware during surgery.

The Physiological Implications of COVID-19 on the Administration of Propofol Anesthesia

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has cast a profound shadow over global healthcare systems, compelling healthcare professionals to reevaluate and adapt various medical procedures and practices. One such aspect is the administration of general anesthesia, with a focus on the commonly used agent, propofol. The physical effects of COVID-19 on the administration of propofol anesthesia are complex and multifaceted, impacting both healthcare providers and patients. This article delves into these effects, shedding light on the challenges and adaptations necessitated by the pandemic.

  • Respiratory Complications and Airway Management

COVID-19 is primarily a respiratory illness that can manifest as pneumonia and acute respiratory distress syndrome (ARDS). Patients with severe COVID-19 often experience reduced lung function, which poses specific challenges during the administration of propofol anesthesia.

Effect on Propofol Dosage: Anesthesia providers may need to adjust the dosage of propofol to account for the compromised respiratory status of COVID-19 patients. Reduced lung function may affect the pharmacokinetics of the drug, requiring a more cautious approach to avoid over-sedation and respiratory depression.

Airway Management: Intubation and extubation, crucial steps in general anesthesia, become more intricate during the pandemic due to the risk of viral transmission. The donning of additional personal protective equipment (PPE) can extend the time needed for these procedures. Healthcare providers must adapt to these challenges to ensure the safe administration of propofol anesthesia.

  • Coagulation Abnormalities and Hemodynamic Changes

COVID-19 is associated with coagulation abnormalities and cardiovascular complications. Patients may present with hypercoagulability and a heightened risk of thrombosis. This can affect the choice of anesthetics and the monitoring of hemodynamic stability.

Choice of Anesthetic Agents: Given the potential for thrombotic complications in COVID-19 patients, anesthesia providers may need to consider alternatives to propofol, which could exacerbate coagulation abnormalities. Regional anesthesia techniques, such as neuraxial anesthesia, might be preferred in some cases.

Hemodynamic Monitoring: Anesthesia providers should be vigilant in monitoring hemodynamic parameters during the administration of propofol anesthesia in COVID-19 patients. The virus’s impact on cardiovascular function necessitates close observation to ensure patient safety.

  • Challenges in Infection Control and Safety

Infection control measures have become paramount during the pandemic, with healthcare providers needing to safeguard against the transmission of the virus in healthcare settings. These measures profoundly influence the administration of propofol anesthesia.

Increased PPE Usage: The use of extensive PPE, including N95 masks, face shields, and gowns, can complicate the work of anesthesia providers. Donning and doffing PPE is time-consuming and necessitates strict adherence to infection control protocols.

Enhanced Sterilization Protocols: Cleaning and sterilization procedures for medical equipment have become more rigorous, including the disinfection of anesthesia workstations and monitoring devices. This meticulous approach to infection control is essential to prevent viral transmission.

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