Mark Welliver

Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent

Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits.

Why capnography for procedural sedation

C apnography is defined by the Free Medical Dictionary (2012) as “monitoring of the concentration of exhaled carbon dioxide in order to assess physiologic status or determine the adequacy of ventilation during anesthesia.” Although often associated with delivery of anesthesia, capnography is gaining application in multiple settings where close monitoring of respiratory and ventilation status is required. Whereas pulse oximetry has gained universal acceptance and become a standard of practice, capnography has been used less extensively outside anesthetizing locations. This column highlights the technology and usefulness of capnography as well as its benefits for use by gastroenterology nurses. Adequate ventilation (movement of gases in and out of the lungs) and resultant respiration (diffusion of gases across alveolar membranes) requires the exchange of oxygen (O2) and carbon dioxide (CO2). Pulse oximetry measures only percentages of blood oxygen levels. Oxygen uptake is only half of the necessary requirements for effective respiration. Carbon dioxide must be removed from the body. Effective respiration requires carbon dioxide to be removed by the exhalation phase of ventilation. If a patient ventilates poorly, carbon dioxide may not be fully exhaled and hypercarbia will develop. Hypercarbia is defined as an arterial blood concentration of carbon dioxide greater than 45 mm Hg (normal 35–45 mm Hg). A small increase in carbon dioxide (1–15 mm Hg) is not usually harmful, but larger increases can result in acidosis, somnolence, and respiratory arrest. Hypercarbia ( 65–70 mm Hg) causes sedation; when this occurs in a patient already sedated with benzodiazepines and narcotics, the two can have an insidious synergy until respiratory arrest occurs. Capnography during procedural sedation and the recovery phase is a prudent consideration. The following scenario highlights the importance of capnography:

Anesthetic Related Advances with Cyclodextrins

Cyclodextrins encapsulate and electrostatically bind to lipophilic molecules. The exterior of cyclodextrins are water-soluble and maintain aqueous solubility despite encapsulation of non-aqueous soluble molecules. This unique ability to encapsulate lipophilic molecules and maintain water solubility confers numerous pharmacologic advantages for both drug delivery and removal. Cyclodextrins, a component part of supramolecular chemistry, may be in its infancy of anesthetic application but recent advances have been described as novel and revolutionary. A review of current research coupled with an understanding of cyclodextrin properties is necessary to fully appreciate the current uses and future potentials of these unique molecules.

Nausea and vomiting: mechanisms and treatment overview.

Much of our current knowledge and understanding of nausea and vomiting (N&V) has been advanced by work in the field of oncology. Chemotherapeutic drugs are toxic agents and have a side effect of N&V. Oncology nurses and physicians have become experts in the treatment of N&V and offer other clinicians much information to aid in our treatment of this undesirable side effect of drugs, procedures, and events. Gastroenterology nurses are often called upon to assess and treat N&V. The causes of N&V are many but, in general, are gastrointestinal, blood borne, or vestibular in origin. Gastrointestinal-originated causes of N&V include gastroparesis, gastric distension, and constipation. Blood-borne causes include drugs and toxins. Vestibular N&V is caused by disruption of the inner ear often initiated by motion. All of these causes trigger a part of the brain called the area postrema (AP) located in the brain stem. The AP is located under the cerebellum, below the 4th ventricle at the level of the medulla oblongata ( Figure 1 ) ( Miller & Leslie, 1994 ). According to Miller and Leslie, “the AP lacks a specific blood–brain diffusion barrier (‘blood–brain barrier’) to large polar (charged) molecules and is thus anatomically positioned to detect emetic toxins in the blood as well as in the CSF [cerebral spinal fluid]” (p. 301). Within the AP is the chemoreceptor trigger zone (CTZ) and the vomiting center. The receptors in these areas cause N&V. Understanding this anatomy and physiology facilitates comprehension of how the drugs and treatments for N&V work and provide a clinical rationale for more effective prevention and treatment. The CTZ is a small area that contains highly sensitive receptors ( Figure 2 ). The receptors that have been identified include serotonin (5HT3), dopamine (D 2 ), acetylcholine (ACh), histamine (H), opioid (mu), cannabinoid (CB1R, CB2R), and substance P neuro-kinnin (NK1) ( National Cancer Institute, 2013 ). Receptors are relatively large protein structures embedded within the lipid membranes that respond to other molecules including neurotransmitters and drugs. Often simply described as a “lock and key fit” between a receptor and another molecule, on an atomic level, it is much more complex. The arrangement of atoms composing the protein receptor is quite

Dopamine antagonists for nausea and vomiting: special considerations.

The dopamine antagonists, particularly droperidol, are effective at treating N&V. Because dopamine plays many roles in the body, especially in the brain, a degree of alteration in mental status should be expected, especially with higher doses. Other less frequent side effects include QT prolongation. When given for non– chemotherapy-induced N&V treatment QT prolongation is rare. Higher doses warrant clinical awareness and ability to identify and treat prolonged QT and its sequelae. Invited authors for a following column will discuss QT prolongation and implications.

Basic airway support for conscious sedation.

In the event of respiratory or airway compromise during sedation procedures, simple maneuvers are often all that is required to reestablish patency and maintain ventilation with adequate oxygenation. As discussed in previous columns, sedative and analgesic drugs suppress respiratory rate, rhythm, and depth. The pharmacologic cause of the respiratory suppression is from central nervous system (CNS) depression. Respiratory compromise during conscious sedation is compounded by the anatomic structures of the airway. Sedative agents can cause pharyngeal muscle relaxation, mandible receding (jaw), and posterior tongue displacement, which all contribute to narrowing of the airway with possible occlusion. A patient lying on his or her back or side promotes the chin to drop toward his or her chest, whereas the jaw, tongue, and pharynx tend to relax backward. This airway position is undesirable and may be recognized by hearing the patient snore or grunt. Snoring or grunting represents a partial occlusion of the airway. Lifting the patient’s chin and jaw usually reestablishes a fully patent airway after partial occlusion (see Figure 1). Complete occlusion occurs when the jaw, tongue, and pharyngeal tissues relax backward and block the flow of ventilation. Complete occlusion of the airway may occur despite the appearance of the patient’s chest rising and falling. Elevating the chin may restore normal ventilation in this situation, but complete occlusion represents too deep of sedation for this particular patient. Continued elevation of the chin should be maintained until the patient is able to support his or her own patent airway. The CNS is composed of the brain and spinal cord. The brain can be imagined as having three general levels of consciousness and purpose: (1) higher cognitive functions (alert, awareness, and cerebration), (2) protective functions (awake, fight, or flight response), and (3) the basic brain stem functions (control vital organs, respiration, and heart rate). Conscious sedation goals are targeted at decreasing the higher functions of the brain. It is not desirable to suppress protective reflexes. Unfortunately, sedative agents may affect the protective and basic functions of the brain causing unwanted effects. Located in the brain stem is the respiratory center, which is composed of specialized cells that are highly responsive to hydrogen ions in relation to carbon dioxide levels in the blood stream. As carbon dioxide levels rise in the blood stream, Pharmacology Matters

Successive cases of an entrapped arterial catheter guidewire in separate patients on the same day

To the Editor,We share our recent experiences with the ArrowInternational radial artery catheterization set (Ref RA-04020, Reading, PA, USA). After general anesthesia wasinduced and our patient’s left radial artery was positionedand prepared, we introduced the Arrow catheter set into thesite. Bright red blood was observed in the back flow tubethat houses the guidewire. The guidewire was thenadvanced approximately 1 cm before gentle resistance wasfelt. Attempts at withdrawing the guidewire back into thecatheter set were also met with resistance. Several addi-tional attempts were made at withdrawal using slighttraction and twisting on the guidewire, but without success.The Teflon outer catheter, guidewire, and introducerneedle were then withdrawn together as a unit; however,the guidewire uncoiled, remained secure within the tissues,and could not be removed despite attempts to pull it out.An immediate intraoperative x-ray (Figure) was performed,which showed the intact uncoiled guidewire kinked withinthe tissues. A vascular surgical consult was requested, andafter consultation, a surgical cut-down was performed toretrieve the guidewire that was imbedded 1 cm within thesubcutaneous tissues, but not within the artery. The sitewas closed with two sutures and then the original surgicalprocedure was completed as planned without incident.Coincidently, another incident involving an entrappedguidewire occurred on this same day with another similarArrow catheter kit. In this case, the introducer needleentered the patient’s radial artery, but partial advancementof the guidewire was met with resistance. When with-drawal of the guidewire was met with resistance, the entireapparatus was removed without further guidewire reposi-tioning. This time the catheterization set was removedintact without difficulty.There have been many accounts describing the risk ofguidewire entrapment, uncoiling, and fragmentation,