Since the introduction of regional analgesia, there has been a trend towards reduced morbidity and mortality after open lung resection. Thoracic epidural analgesia is commonly achieved with a continuous infusion of a local anesthetic alone or in combination with an opiate. In order to reduce the volume required to produce an effect and lessen the chance of hypotension and motor weakness, the catheter is usually placed as close as possible to the dermatomes to be covered. A low concentration of local anesthetic such as 0.1% or 0.05% bupivacaine hydrochloride combined with an opiate (e.g., fentanyl 5 to 10 µg per mL, hydromorphone 8 µg per mL, or sufentanil 0.1 µg per mL) produces synergistic effects with a reduction of the sympathetic blockade associated with the use of a more concentrated local anesthetic alone. In addition, the presence of local anesthetics seems to increase the affinity of the narcotic for the opioid receptors. Potential complications of thoracic epidural technique can be related to the placement (inadvertent dural puncture, trauma to the spinal cord, hematoma) or drug administration (intravascular injection of local anesthetics with resultant cardiovascular and central nervous system toxicity). Long-acting antiplatelet medications discontinuation should follow the American Society of Regional Anesthesia and Pain Medicine guidelines to prevent neuraxial hematomas.

Paravertebral blocks and catheters can be used preoperatively or postoperatively, in combination with parenteral opiates and NSAIDs, as an alternative to thoracic epidural analgesia. To be effective, multiple levels need to be blocked unless a catheter is placed. The failure rate for the blind technique is relatively high (6% to 10%) and can be decreased by locating the space via ultrasound guidance or under direct vision by the surgeon before closing the chest. Pneumothorax (especially if bilateral blocks are attempted), hypotension, local anesthetic toxicity due to the high vascularity of the area, and inadvertent total spinal are all potential risks. Advantages compared with epidural analgesia include less hypotension, less nausea or vomiting, and the ability to block just the surgical side.

Intrathecal injection of opiates can be used pre- or intraoperatively for an 18- to 24-hour postoperative pain relief. However, when compared to epidural injection, intrathecal opiates (i.e., morphine) are associated with an increased incidence of late respiratory depression (4% to 7% compared to less than 1% for epidural administration), pruritus, nausea and vomiting, which could increase length of stay (LOS) in the postoperative period.

The advantages of neuraxial techniques compared to systemic opiates include selective blockade of spinal pain receptors with minimal sympathetic blockade, no loss of motor function, and greater predictability of pain relief. Epidural opiates in combination with local anesthetics block the presynaptic and postsynaptic neuron cells of the substantia gelatinosa of the spinal cord by passive diffusion across the dura into the cerebrospinal fluid. The lipophilic narcotics, such as fentanyl 0.1 mg, methadone 5 mg, and meperidine 30 to 100 mg, have a relatively short onset of action (less than 12 minutes). They provide significant pain relief in 20 to 30 minutes, which can last for 6 to 7 hours. In contrast, a hydrophilic opiate such as morphine (5-mg dose) has a relatively slow onset of action (15 to 30 minutes), provides maximal pain relief in 40 to 60 minutes with a duration of action of more than 12 hours. Other side effects include urinary retention, pruritus, nausea, and vomiting. The narcotic antagonist naloxone can reverse all the aforementioned side effects but will also reverse the analgesia, so it must be used cautiously. Overall, unlike epidural local anesthetic, epidural opioids have not been shown to decrease the incidence of postoperative respiratory complications.

Peripheral nerve blocks with long-acting local anesthetics can be used to control pain after thoracoscopy or thoracotomy. The duration of single injections is relatively short (6 to 8 hours when bupivacaine hydrochloride is used). Catheters can be left in place and dosed postoperatively. Intercostal nerve blocks can be done under direct vision by the surgeon before closing the chest cavity or percutaneously before awakening the patient. The intercostal nerves to be blocked are at the level of the incision and two or three interspaces above and below. Of the three main sensory divisions of the intercostal nerve (posterior, lateral, and anterior cutaneous nerve), the posterior branch cannot be blocked with this approach, limiting its usefulness in the case of a posterolateral incision. There is controversy on the quality of analgesia with this technique alone when compared with the epidural route. Intercostal catheters are indicated as part of a multimodality treatment when neuraxial blocks are contraindicated (e.g., patients on anticoagulation or tumor involvement of the epidural space) or for minimally invasive procedures. Recently, serratus plane and erector spinae block and catheters have been described as good analgesic options for minimally invasive lung resections. Ultrasound guidance makes these blocks relatively easy and with low risks of complications.

The use of extended-release formulation of liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc, Parsippany, NJ) may increase the duration of the block, improving the quality of analgesia, especially when paired with other adjuvants. Because of the relatively high rate of systemic absorption of the local anesthetic from the intercostal space, there is an increased risk of systemic toxicity. Liposomal bupivacaine has been used off label for intercostal nerve blockade and other peripheral nerve blocks. The few case reports where the medication was used did not show permanent nerve damage or toxicity, whereas the degree of analgesia was reported comparable to thoracic epidural. Due to the concern of systemic toxicity, the use of liposomal bupivacaine in a peripheral nerve block precludes the use of local anesthetic via neuraxial blockade.

Systemic administration of opioids was the main analgesic modality in the past, alone or as part of a multimodal approach, especially for minimally invasive surgical procedures. With the advent of Enhanced Recovery after Thoracic Surgery (ERATS) protocols and the current opioid epidemic affecting the United States, there has been a shift in the analgesic paradigm in favor of a multimodal approach based on regional techniques and nonopioid medications, leaving opioids as a rescue. Sedation, potential respiratory depression, hypoventilation, inhibition of cough, and reduced sighing are the main side effects that can prolong LOS.

NSAIDs such as ketorolac, diclofenac, ketoprofen, and indomethacin can be used as adjuvants to parenteral opiates, particularly for the treatment of shoulder pain associated with chest tube placement. Potential side effects for NSAIDs include gastric bleeding, platelet dysfunction, and renal insufficiency in patients who are severely fluid restricted, especially the elderly. Intravenous acetaminophen is used in the US can be added to potentiate analgesia if not contraindicated.

Low-dose intravenous ketamine infusion (0.25 mg/kg/hr) has been used as an adjuvant in the perioperative period, especially in patients with chronic pain. Psychomimetic side effects are a possibility but are rare at this dosage. Intravenous dexmedetomidine can be used intraoperatively to potentiate analgesia. The recommended dose is a continuous infusion of 0.2 to 0.7 (to a maximum of 1.5) µg/kg/hr without loading. Its central ₂-agonism potentiates analgesia, allowing a decrease in the dose of intravenous narcotics and decrease the minimal alveolar concentration (MAC) of general anesthesia. Hypotension and bradycardia are potential side effects as well as sedation. Lidocaine infusion (1.0 to 1.5 mg/kg/hr) can also be used as an adjuvant. Despite the concern of systemic toxicity, there has been no reports of such complication. Intravenous lidocaine infusion should be considered as an alternative when neuraxial blockade is contraindicated or for minimally invasive procedures.