Introduction
The successful treatment of pain in the preoperative patient is important with all surgical specialties, but in many instances it is more critical in the patient undergoing neurosurgical or spinal based surgeries. Attention to the hemodynamic swings associated with pain in the immediate postoperative period, with mindful management, sets the patient up for an expedited and uncomplicated recovery. Acute pain can commonly increase sympathetic tone, leading to hypertension, tachycardia, and increased intracranial pressure.
In a comprehensive, retrospective review of postoperative pain, comparing those undergoing intracranial surgery to those with select extracranial procedures, the intracranial group did have significantly less pain than the comparison group ( p < 0.05). A subset of intracranial patients did, however, have significantly more pain than others in the group: those requiring frontal craniotomies required more opioids and had elevated heart rates, blood pressure, and intracranial pressure (ICP). The analysis was inconclusive regarding those undergoing intracranial procedures. Notwithstanding, some studies suggest that a large volume local anesthetic block in the cranium prior to incision may lower the overall opioid requirements in the postoperative period. This has not been substantiated in a prospective fashion. It is well substantiated that spinal neurosurgery is more painful than after craniotomy.
There are many inherent factors managing pain in the neurosurgical group; these include the desire to limit postoperative sedation, as it is clinically imperative to reliably obtain an accurate neurologic exam to guide treatment, as the surrogate monitors are secondary measures of neurologic function, and have inherent flaws. This gold-standard monitor of a cogent and uncompromised neurologic assessment can be affected adversely if the patient is sedated or obtunded. Employing medications with pharmacokinetically short half-lives can help remedy the paradox by keeping patients sedated when needed and awake when an exam is warranted. This strategy, however, is not without consequence and can result in cumulative effects of the infusion. This conflict of treatment goals can lead to the withholding of pain medication and pain management techniques, which also creates a poor patient outcome. In some instances, this has created an interest in the use of mixed agonist/antagonist or partial agonist opioids. The assertion that these are innately safer, however, is a misconception, and the respiratory depression created with these agents is hard to reverse with opioid antagonists and may lower the ceiling of pain control through opioid agonism. Opioids used inappropriately can, with their known side-effect profiles of cough, nausea, vomiting, and respiratory depression, increase patient morbidity and mortality, as one may suspect that this could raise intracranial pressure.
Fairly regularly, waking the patient up in the operating room to demonstrate retained (or improved) motor and cognitive function is commonplace, despite intraoperative use of sensory and motor system monitors (SSEPS, MEPS). The use of rapidly acting intraoperative intravenous or inhalational anesthetics has led to the potential paradigm of an awake patient with poor analgesia. Two points deserve a mention: (1) the anesthetic plan needs to be clearly defined to the patient, setting expectations; and (2) the need for an awake patient does not mean that they cannot have pain control. The anesthesia plan should include both intraoperative and postoperative planning to ensure adequate analgesia, despite a reliable neurologic assessment; one does not preclude the other.
Pain care in the postoperative period needs to be based on pain treatment as the primary goal. Although the hemodynamic consequences of pain, including heart rate and blood pressure, can be treated with sympatholytics (β-blockers, etc.), this obviously provides inappropriate analgesia. Studies have shown that pain in the postoperative period can adversely influence patient outcome independent of hemodynamic or intracranial endpoints. Proper pain control may stabilize hemodynamics, reduce blood pressure, and lower CMRO 2 (cerebral metabolic oxygen consumption), as well as lower the ICP. In addition to the pain issues, the perioperative period in the intracranial patient is complex, and needs to be considered systemically, as the question becomes: how far reduced is the intracranial compliance? The surgical stress response causes elevations in body oxygen consumption and serum catecholamine concentrations. Systemic hypertension is often present after neurosurgical procedures and has been linked to intracranial hemorrhage. Bleeding in the postoperative period can lead to increased mortality, morbidity, and hospitalization. The cerebral consequences of the recovery period can lead to cerebral hyperemia and increased ICP. Prevention or control of pain is one of the major factors in limiting these adverse systemic effects.
Over the last decade or so, developments in intravenous opioids, new regional techniques, and local anesthetics have greatly enhanced our abilities to treat this patient group. Preemptive analgesia may lead to the improved stability of the patient throughout the surgical experience. To minimize pain and decrease the stress response and hemodynamic changes, the surgeon and anesthesiologist must function together to provide optimal care.
Philosophically, the presence of pain and the body’s reaction to it can be altered by many strategies. The opportunity for interruption of the pain pathway can be divided into four components: transduction, transmission, modulation, and perception. Transduction occurs when one type of energy (temperature, mechanical) is converted to electrical energy via ionic charge separation, that is, action potentials. Secondly, transmission is the transfer of pain impulse through the nervous system by the first order, second order, and third order neurons via the C and A delta fibers through the spinothalamic tracts to the thalamus and cortex. Pain modulation describes the alteration of the pain signal (either augmentative or diminish) as it travels. Perception is the subjective and emotional interpretation of pain, occurring in the somatosensory cortex and limbic system. The patient’s genetic, social, and cultural backgrounds influence this interpretation. The remaining sections of this chapter focus on key points to enhance outcomes, patient satisfaction, and patient safety.
Acute pain management assessment
Anesthesia management begins with appropriate preoperative planning. Several factors need to be assessed: the importance of reducing anxiety, the pain treatment history, and an evaluation of any comorbidities that may influence the response to, or management of the planned pain care.
Chronic long-term opioid use for chronic pain makes determining the baseline dose for opioids in the management of chronic pain patients somewhat difficult. Predictably, physical tolerance and dependence occurs. The analgesic tolerance to opioid medication can influence dosing in both the intraoperative anesthetic and postoperative pain course. It is important to realize that the use of chronic medications is for a stable pain condition and it will be necessary to supplement this baseline dose with additional medication. It is well established that patients with chronic opioid use become tolerant to the opioid effects of nausea, vomiting, sedation, euphoria, and respiratory depression, where there is minimal tolerance to papillary constriction and constipation. Regional anesthesia is very helpful in mitigating the need for a largely weighted opioid pain care regimen. This includes intracranial field blocks to help reduce the opioid requirement postoperatively.
Patient controlled analgesic regimens are also helpful, reducing the lag time between the patient requesting and obtaining an analgesic dose of medicine. Studies suggest the overall dose is lower and pain control is improved when employing these therapies, either the PCIA (patient controlled intravenous analgesia), the PCEA (patient controlled epidural analgesia) or the PCRA (patient controlled regional analgesia). With the aid of ultrasound guidance, regional analgesia has become a major player in the acute and subacute pain management phase of recovery, providing dense pain coverage while reducing the risk of neuraxial bleeding or infection. When employing neuraxial regional analgesia, it is important to acknowledge and consider the bleeding risks, as outlined in the most recent version of the American Society of Regional Analgesia Recommendations on anticoagulant management for regional analgesia.
Consideration for organ system-specific influences on the anesthetic plan is essential. A patient with renal disease is prone to complications from drugs with metabolites removed by the kidneys. Meperidine, for example, breaks down to normeperidine, which has the potential to reduce the seizure threshold. Some opioids have active metabolites that should be considered. Morphine and hydromorphine are metabolized to M3G/M6G and H3G/M6G, respectively, and are renally excreted. The 6-glucoronide metabolite is pharmacologically active at the mu receptor, while the 3G metabolite has been implicated in lowering the seizure threshold and reducing unwanted side effects.
Opioids predictively can contribute to the slowing of the gastrointestinal system through a mu-mediated mechanism, while regional or local analgesia can cause increased peristalsis and surgical neuroaxial anesthesia can exacerbate ileus. In these cases, it is important to implement a bowel support regimen as a standard part of the program when using intravenous or oral opioids or epidural infusions. Further, a history of urinary retention may cause concern for regional neuroaxial analgesia as neuroaxially administered opioids and local anesthetics can cause urinary retention.
Acute pain management assessment
Anesthesia management begins with appropriate preoperative planning. Several factors need to be assessed: the importance of reducing anxiety, the pain treatment history, and an evaluation of any comorbidities that may influence the response to, or management of the planned pain care.
Chronic long-term opioid use for chronic pain makes determining the baseline dose for opioids in the management of chronic pain patients somewhat difficult. Predictably, physical tolerance and dependence occurs. The analgesic tolerance to opioid medication can influence dosing in both the intraoperative anesthetic and postoperative pain course. It is important to realize that the use of chronic medications is for a stable pain condition and it will be necessary to supplement this baseline dose with additional medication. It is well established that patients with chronic opioid use become tolerant to the opioid effects of nausea, vomiting, sedation, euphoria, and respiratory depression, where there is minimal tolerance to papillary constriction and constipation. Regional anesthesia is very helpful in mitigating the need for a largely weighted opioid pain care regimen. This includes intracranial field blocks to help reduce the opioid requirement postoperatively.
Patient controlled analgesic regimens are also helpful, reducing the lag time between the patient requesting and obtaining an analgesic dose of medicine. Studies suggest the overall dose is lower and pain control is improved when employing these therapies, either the PCIA (patient controlled intravenous analgesia), the PCEA (patient controlled epidural analgesia) or the PCRA (patient controlled regional analgesia). With the aid of ultrasound guidance, regional analgesia has become a major player in the acute and subacute pain management phase of recovery, providing dense pain coverage while reducing the risk of neuraxial bleeding or infection. When employing neuraxial regional analgesia, it is important to acknowledge and consider the bleeding risks, as outlined in the most recent version of the American Society of Regional Analgesia Recommendations on anticoagulant management for regional analgesia.
Consideration for organ system-specific influences on the anesthetic plan is essential. A patient with renal disease is prone to complications from drugs with metabolites removed by the kidneys. Meperidine, for example, breaks down to normeperidine, which has the potential to reduce the seizure threshold. Some opioids have active metabolites that should be considered. Morphine and hydromorphine are metabolized to M3G/M6G and H3G/M6G, respectively, and are renally excreted. The 6-glucoronide metabolite is pharmacologically active at the mu receptor, while the 3G metabolite has been implicated in lowering the seizure threshold and reducing unwanted side effects.
Opioids predictively can contribute to the slowing of the gastrointestinal system through a mu-mediated mechanism, while regional or local analgesia can cause increased peristalsis and surgical neuroaxial anesthesia can exacerbate ileus. In these cases, it is important to implement a bowel support regimen as a standard part of the program when using intravenous or oral opioids or epidural infusions. Further, a history of urinary retention may cause concern for regional neuroaxial analgesia as neuroaxially administered opioids and local anesthetics can cause urinary retention.
Systemic medications for acute pain management
In very rare situations general anesthesia with volatile anesthetics plays a role in the postoperative or acute pain management plan. Resting the brain after injury or surgery is sometimes required and typically involves an intravenous anesthetic route; however, an appreciation for the difference in hemodynamics and CMRO 2 consumption may make it advantageous in certain cases. The use of these drugs in limiting the stress response is restricted because of the effects that higher concentrations can have on CBF, cerebral blood volume, and ICP.
Etomidate
When given by the intravenous route, etomidate may have some ability to blunt the adrenocortical system’s response to stress. This effect is seen in the blunting of the rise in cortisol expected with similar tissue trauma. Etomidate is thought to accomplish this by blocking enzymes in the cortisol synthesis pathway. The clinical benefit of this drug has not been proved in prospective randomized trials. Its long recovery time may also limit its use as a neuroanesthetic agent. Long-term administration can cause an Addisonian presentation and should be avoided.
Ketamine
Ketamine can raise the CMRO 2 at anesthetic doses, but may be helpful as an adjuvant at very low doses to a refractory pain patient. Caution needs to be exercised when employing this medication in the pain care regimen of the neurosurgical patient.
Opioids
Recent years have shown a dramatic increase in the utilization of high-potency short-acting opioids. Half-lives, distribution properties, and side effects play a role in the decision to use opioids in the management of the postoperative patient. The choice depends on the need for a neurologic examination, the comorbidities of the patient, and the anticipated length of infusion.
Propofol
Propofol has been used to try to limit the wake-up time from general anesthesia and to blunt the initial stress and pain responses. Long-term administration needs caution, as propofol infusion syndrome can occur in doses of 4–5 mg/kg/h for as little as 48 hours, heralded by metabolic acidosis, rhabdomyolysis, acute renal failure, and cardiac failure. The treatment is supportive and includes cessation of propofol.
Alpha2-Adrenergic Agonists
Dexmedetomidine is a highly selective alpha2 agonist (1620:1), as compared to clonidine (220:1) alpha2 to alpha1. Both clonidine and dexmedetomidine attenuate the response to laryngoscopy and reduce the MAC, but both can cause hypotension, which needs to be mitigated in low compliant, pressure-dependent cerebral blood flow clinical scenarios. Dexmedetomidine provides sedation, anxiolysis, potent analgesia, and spontaneous breathing. Clonidine has been used in patients with brain trauma and after extensive neurologic surgery to blunt the stress response. The drug has also been shown to blunt the possibilities of vasogenic edema. The use of spinal or epidural alpha-adrenergic blockade has also been shown to reduce the stress response. It is unclear whether the reduction in adrenergic response with epidural or intrathecal clonidine is a direct effect of the alpha-adrenergic blockade or a response to the clonidine-induced analgesia. The use of systemic beta-adrenergic and alpha-adrenergic agents has been shown to stabilize the hemodynamic response and the cerebral circulation.
Nonsteroidal Anti-Inflammatory Drugs
The perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) may enhance the ability of other techniques such as regional analgesia and anesthesia in blocking the stress response. The enhancement of regional analgesia and anesthesia is related to the NSAIDs’ action at peripheral receptors involved in the tissue trauma cascade, along with central mechanisms, including prostaglandin reduction. Caution needs to be exercised in treating patients with known renal, cardiovascular, or gastrointestinal comorbidities. NSAIDs can interfere with platelet aggregation. Furthermore, NSAIDS may affect bone healing and have been implicated in failed lumbar fusions, although retrospective reviews failed to demonstrate significance. Cyclooxygenase-2 (COX-2) inhibitors have been implicated with increasing cardiac morbidity when taken long-term; however, acute perioperative administration data are lacking.
Neuropathic Pain Agents
Anticonvulsants are often used after intracranial surgery to prevent seizures. These drugs may also offer some improvement in neuropathic pain syndromes and reduce the opioid requirements. The classic drugs used for neuropathic pain, of the anticonvulsant class, include gabapentin, pregabalin, carbamazepine, oxycarbazepine, lamictal, and topiramate. Baclofen, a GABA-B agonist, has been used to treat spinal-induced spasticity and has been reported in some patients to improve pain of neuropathic origin. Antidepressant neuropathic pain agents include duloxetine, amitriptyline, nortriptyline, venlafaxine, to name a few. These function not as ion channel blockers, but mostly as neurotransmitter reuptake inhibitors. Caution should be exercised, as they can interfere with platelet aggregation and have the potential to contribute to bleeding.
Regional analgesic options
Neuroaxial Epidural Infusion Therapy
The use of epidural infusion therapy has increased in recent years as a primary method of acute pain control in patients undergoing surgical procedures involving peripheral nerves. The proper use of an epidural infusion requires a working knowledge of dermatomal anatomy, drug pharmacokinetics, drug synergies, and postoperative follow-up requirements. Several factors promote the need for success: it is essential to place the catheter congruent with the patient’s site of pain. Pharmacokinetically, the potency is greater when medications are delivered epidurally versus intravenously. Redistribution occurs creating untoward, unwanted side effects. The physiochemical properties of the epidural agent chosen can influence the drug’s distribution. A lipophilic drug such as fentanyl requires placement of the catheter at a level near the nerve innervation of the surgical site. With morphine, which is much less lipid soluble, the catheter placement is less critical because the drug may cover several interspaces prior to being absorbed. Hydromorphone has intermediate properties. Further, for more than a decade, data have demonstrated an antinociceptive synergy between intrathecal morphine and local anesthetics during visceral and somatic nociception at dosages that do not impair motor function. The combination of local anesthetics and opioids offers a synergistic effect that leads to better analgesia than either drug infused alone. Local anesthetic infusion therapy has been shown to be the most effective method of blunting the stress response to tissue trauma. The addition of opioids helps eliminate the problem of tachyphylaxis that may develop with local anesthetics alone.
Peripheral Nerve Blockade
Peripheral nerve infusions of local anesthetic can be beneficial in the intraoperative period as well as for postoperative pain control. Common sites for continuous infusion include the brachial plexus and the femoral nerve. A nerve stimulator or ultrasound is helpful in guiding the proper placement of the catheter. In general, a blunt-tipped needle is preferable to a sharp bevelled needle to reduce the risk of nerve injury.
Complications of neuroanesthesia pain management
Mental Status Changes
Serial neurologic checks are often an essential part of the postoperative course. If pain treatment interferes with this assessment, the overall benefit of the pain treatment may be lost. Establishing a team approach with the surgical team and the nursing team to balance the risks and benefits of pain therapies is crucial.
Elevation of Arterial Carbon Dioxide
The importance of ICP varies in the neurosurgical population. In patients in whom this is an important factor, it is crucial to have some method of monitoring postsurgical carbon dioxide (CO 2 ). Despite the benefits of improved hemodynamics in ensuring the stability of the patient with elevated ICP, the risk of excessive sedation and hypercarbia could be a problem, and the patient must be watched closely. Arterial CO 2 and pH are ways to monitor for possible complications and may be early indicators of impending problems.
Reduction of Arterial Oxygen
Hypoxemia may create multiple problems in the patient with neuronal tissue trauma. Anaerobic metabolism occurs when neurons do not have enough oxygen substrate, which can result in a reduction of adenosine triphosphate and subsequent cell death. The use of supplemental oxygen and oxygen saturation, as well as serial arterial blood gas monitoring, is essential in patients receiving systemic opioids.
Hypotension
In the patient with possible spinal cord trauma, the use of regional anesthesia can be helpful in controlling the stress response and subsequent systemic changes. The resultant decrease in mean arterial pressure can decrease perfusion to the neurologic tissue and create ischemia. Careful attention to blood pressure is crucial when using local anesthetics postoperatively.
Cerebrospinal Fluid Leak
The chance of subarachnoid puncture when placing an epidural catheter must be weighed against the benefit of the catheter. The risks of brain herniation must also be discussed with the surgeon if there is any intracranial disease process. Placing the catheter intraoperatively may be helpful in certain situations.
Nerve Injury
When using regional techniques in those with coexisting neurologic disease, a risk of nerve injury exists if the patient has abnormal nociception in the area of the proposed procedure. This risk also exists for the patient under general anesthesia or heavy sedation who may be unable to respond to inadvertent intraneural injection.
Infection
In the sedated patient, aspiration precautions should be ordered. This should be accompanied by frequent neurologic checks. If aspiration is a risk, sedating medications should be used with caution. It goes without saying, however, that regional anesthesia should be avoided in the patient with local infection at the site of the proposed regional procedure or systemic infection. Vigilance once the catheter is placed is also essential, reducing the chance of it becoming a nidus for infection.
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